Background: Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.
View Article and Find Full Text PDFSomatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: 'pseudo-diploid' cells harboring few SCNAs and highly aneuploid cells.
View Article and Find Full Text PDFCardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate around 0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.
View Article and Find Full Text PDFAim: While manual quantification is still considered the gold standard for skeletal muscle histological analysis, it is time-consuming and prone to investigator bias. To address this challenge, we assembled an automated image analysis pipeline, FiNuTyper (Fiber and Nucleus Typer).
Methods: We integrated recently developed deep learning-based image segmentation methods, optimized for unbiased evaluation of fresh and postmortem human skeletal muscle, and utilized SERCA1 and SERCA2 as type-specific myonucleus and myofiber markers after validating them against the traditional use of MyHC isoforms.
Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS.
View Article and Find Full Text PDFProstate cancer is a heterogeneous disease with a need for new prognostic biomarkers. Human leukocyte antigen (HLA) genes are highly polymorphic genes central to antigen presentation to T-cells. Two alleles, HLA-A*02:01 and HLA-A*24:02, have been associated with prognosis in patients diagnosed with de novo metastatic prostate cancer.
View Article and Find Full Text PDFPhysiological liver cell replacement is central to maintaining the organ's high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon (C) birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age <3 years). Hepatocyte renewal is highly dependent on the ploidy level.
View Article and Find Full Text PDFHeart failure is a leading cause of death that develops subsequent to deleterious hypertrophic cardiac remodelling. MAPK pathways play a key role in coordinating the induction of gene expression during hypertrophy. Induction of the immediate early gene (IEG) response including activator protein 1 (AP-1) complex factors is a necessary and early event in this process.
View Article and Find Full Text PDFVitreous fluid is commonly collected for toxicological analysis during forensic postmortem investigations. Vitreous fluid is also often analyzed for potassium, sodium, chloride and glucose for estimation of time since death, and for the evaluation of electrolyte imbalances and hyperglycemia, respectively. Obtaining such results in the early phase of a death investigation is desirable both in regard to assisting the police and in the decision-making prior to the autopsy.
View Article and Find Full Text PDFThe identification of unknown human remains represents an important task in forensic casework. If there are no clues as to the identity of the remains, then the age, sex, and origin are the most important factors to limit the search for a matching person. Here, we present the outcome of application of so-called bomb pulse radiocarbon (C derived from above-ground nuclear bomb tests during 1955-1963) analysis to birthdate human remains.
View Article and Find Full Text PDFBackground: Accidental hypothermia results in various dysfunctions in the human body. Additionally, coagulation disorder can lead to a life-threatening condition. We previously demonstrated that platelets stored in the spleen were activated and thus triggered coagulation disorder in a mouse model of hypothermia.
View Article and Find Full Text PDFThe role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects.
View Article and Find Full Text PDFChronic alcohol abuse causes cognitive impairments associated with neurodegeneration and volume loss in the human hippocampus. Here, we hypothesize that alcohol reduces the number of granule cells in the human dentate gyrus and consequently contribute to the observed volume loss. Hippocampal samples were isolated from deceased donors with a history of chronic alcohol abuse and from controls with no alcohol overconsumption.
View Article and Find Full Text PDFThe aim was to assess the activation and association of the NF-κB system across synovial membrane (SM) and articular cartilage (AC) in patients with knee osteoarthritis (OA) and ascertain its potential effects on catabolic mediator expression in advanced OA. SM and AC were obtained from 40 OA patients undergoing total knee arthroplasty and from 19 postmortem control subjects. NF-κB subunit RelA in nuclear and cytosolic fractions and NF-κB1-DNA binding in nuclear extracts was assessed by ELISA, whereas , , , , and gene expression were analyzed by reverse transcriptase-quantitative PCR in tissues.
View Article and Find Full Text PDFIn animal studies, impaired adult hippocampal neurogenesis is associated with behavioral pathologies including addiction to alcohol. We hypothesize that alcohol abuse may have a detrimental effect on the neurogenic pool of the dentate gyrus in the human hippocampus. In this study we investigate whether alcohol abuse affects the number of proliferating cells, stem/progenitor cells, and immature neurons in samples from postmortem human hippocampus.
View Article and Find Full Text PDFVascular changes, including blood brain barrier destabilization, are common pathological features in multiple sclerosis (MS) lesions. Blood vessels within adult organs are reported to harbor mesenchymal stromal cells (MSCs) with phenotypical and functional characteristics similar to pericytes. We performed an immunohistochemical study of MSCs/pericytes in brain tissue from MS and healthy persons.
View Article and Find Full Text PDFThe hematopoietic system seeds the CNS with microglial progenitor cells during the fetal period, but the subsequent cell generation dynamics and maintenance of this population have been poorly understood. We report that microglia, unlike most other hematopoietic lineages, renew slowly at a median rate of 28% per year, and some microglia last for more than two decades. Furthermore, we find no evidence for the existence of a substantial population of quiescent long-lived cells, meaning that the microglia population in the human brain is sustained by continuous slow turnover throughout adult life.
View Article and Find Full Text PDFDifferences in white adipose tissue (WAT) lipid turnover between the visceral (vWAT) and subcutaneous (sWAT) depots may cause metabolic complications in obesity. Here we compare triglyceride age and, thereby, triglyceride turnover in vWAT and sWAT biopsies from 346 individuals and find that subcutaneous triglyceride age and storage capacity are increased in overweight or obese individuals. Visceral triglyceride age is only increased in excessively obese individuals and associated with a lower lipid removal capacity.
View Article and Find Full Text PDFCardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood.
View Article and Find Full Text PDFBiochim Biophys Acta Gen Subj
February 2017
Background: Neuropeptide precursors are traditionally viewed as proteins giving rise to small neuropeptide molecules. Prodynorphin (PDYN) is the precursor protein to dynorphins, endogenous ligands for the κ-opioid receptor. Alternative mRNA splicing of neuropeptide genes may regulate cell- and tissue-specific neuropeptide expression and produce novel protein isoforms.
View Article and Find Full Text PDFThe magnitude of cardiomyocyte generation in the adult heart has been heavily debated. A recent report suggests that during mouse preadolescence, cardiomyocyte proliferation leads to a 40% increase in the number of cardiomyocytes. Such an expansion would change our understanding of heart growth and have far-reaching implications for cardiac regeneration.
View Article and Find Full Text PDFThe contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood).
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