top of page

Group

Public·92 members

Map Of The Human Heart(1992) BEST



"Map of the Human Heart" tells a soaring story of human adventure - adventure of the best kind, based not on violence, but on an amazing personal journey. It is incredible sometimes what distances can be traveled in a single human life, and this is a movie about a man who could not have imagined his end in his beginning.




Map of the Human Heart(1992)



The heart is a central human organ and its diseases are the leading cause of death worldwide, but an in-depth knowledge of the identity and quantity of its constituent proteins is still lacking. Here, we determine the healthy human heart proteome by measuring 16 anatomical regions and three major cardiac cell types by high-resolution mass spectrometry-based proteomics. From low microgram sample amounts, we quantify over 10,700 proteins in this high dynamic range tissue. We combine copy numbers per cell with protein organellar assignments to build a model of the heart proteome at the subcellular level. Analysis of cardiac fibroblasts identifies cellular receptors as potential cell surface markers. Application of our heart map to atrial fibrillation reveals individually distinct mitochondrial dysfunctions. The heart map is available at maxqb.biochem.mpg.de as a resource for future analyses of normal heart function and disease.


Relatively little is known about the protein composition of the different regions and cell types of the heart. Previous studies have focused on defining differences between specific regions of the heart, or single-diseased heart compartments5, or from nonhuman, or subcellular material6,7. Phosphoproteomic studies have also been applied for the analysis of mammalian hearts8,9. Moreover, other studies use transcriptomic approaches10,11,12, which is an imperfect proxy for protein levels and their dynamics. However, proteins are the driving forces of the cellular machinery and they are involved in the control of virtually all physiologic events. The high dynamic range of the muscle proteome presents a formidable challenge to the comprehensive analysis of the heart at the level of expressed proteins. This is because very abundant proteins make it difficult to detect low abundant regulatory proteins in the same sample. The majority of studies only identified a few thousand proteins, and there is a paucity of studies of the human, nondiseased heart, because of the difficulty in obtaining the relevant tissue.


The quantitative landscape of the human heart proteome. a Experimental design, including the source of material (upper panel), in-depth vs. single-run analyses (middle panel), and schematic depiction of the analytical workflow (lower panel). b Graphical illustration of the human heart showing the total number of quantified proteins in each region. c Quantified proteins in three cardiac cell types and adipose fibroblasts. d Bar plot of the total number of quantified proteins in all heart regions, cell types, and the entire data set


Myocardial infarction remains one of the largest causes of death and although rapid ELISA tests against cardiac troponins TNNT2 and TNNI3 play a crucial role, further improvements in diagnosis would be of great clinical benefit42,43. Here, we found that TNNT2 was more abundant (>twofold) than TNNI3 in all cavities and that their expression largely correlated across regions (Pearson correlation: 0.99). Interestingly, the cardiac isoform myosin-binding protein C3 (MYBPC3), which participates in stabilizing sarcomere structures, displayed a strikingly similar protein expression profile to cardiac troponins and was similarly abundant to TNNT2 (about 1.5-fold higher abundant) (Supplementary Fig. 8). Moreover, it can be detected by antibody- and MS-based approaches in human plasma after myocardial injury44,45, showing that it can be used as an useful additional parameter to monitor myocardial infarct.


Globally, 609 (5.8%) proteins were specifically enriched in CFs compared to AFs, ECs, and SMCs. These encompassed 25 cell membrane receptors (Supplementary Data 8). The presence of the tyrosine kinase ROR1 in CFs has not been reported before but we found it to be 200-fold more abundant than in the other cardiac cell types. Activin receptor ACVR1 is required for normal heart development60 and it was also one of the most highest expressed proteins in CFs. Natriuretic peptide receptor NPR3 has a central role in vasodilatation, is known to be present in CFs,61 and our data showed sixfold higher expression in CFs. The drug target hepatocyte growth factor receptor MET, was also increased in CFs (fourfold higher than ECs and SMCs). BDKRB2, the receptor for bradykinin plays a pivotal role in the cardiovascular system by regulating blood pressure. Interestingly, we exclusively identified it in fibroblasts, with 11-fold higher expression in CFs compared to AFs. Likewise, protein levels of the cell membrane phosphatase PTPRZ1 were more than 40-fold higher in CFs compared to all other investigated cell types, a finding supported by qPCR. Interestingly, the direction of expression changes was concordant between the mRNA and protein levels. Importantly, however, for this and six other genes, the fold-changes indicated by qPCR were not predictive of the actual protein-level changes (Fig. 5d). Our data provide a catalog of CF-enriched marker candidates that hold promise for better definition and targeting of human CFs.


Clinical application of the healthy human heart atlas to atrial fibrillation. a Experimental workflow: LA tissues from three atrial fibrillation patients (AFib) were single-runs of technical triplicates. Data were matched against the healthy human LA library. b Volcano plot of the p values vs. the log2 protein abundance differences in AFib compared to healthy LA. Significantly up- and downregulated proteins are highlighted in red and blue, respectively (FDR 0.05)


Tandem mass spectra were searched against the 2015 Uniprot human databases (UP000005640_9606 and UP000005640_9606_additional) using MaxQuant21 version 1.5.5.6 with a 1% FDR at the peptide and protein level, peptides with a minimum length of seven amino acids with carbamidomethylation as a fixed modification, and N-terminal acetylation and methionine oxidations as variable modifications. Enzyme specificity was set as C-terminal to arginine and lysine using trypsin as protease and a maximum of two missed cleavages were allowed in the database search. The maximum mass tolerance for precursor and fragment ions was 4.5 ppm and 20 ppm, respectively. If applicable, peptide identifications by MS/MS were transferred between runs to minimize missing values for quantification with a 0.7-min window after retention time alignment. Label-free quantification was performed with the MaxLFQ algorithm using a minimum ratio count of 1. For clinical AFib samples, the identification transfer was restricted to the healthy LA library only, and we set a minimum ratio count of 2 for label-free quantification.


alien 3, anne parillaud, ben mendelsohn, cinema, dresden, dresden bombing, film review, film reviews, filmmaking, films, greg moss, hieronymus bosch, hieronymus bosch hell, jason scott lee, map of the human heart, map of the human heart 1992, map of the human heart movie, mossfilm, movie, movie review, movie reviews, movies, patrick bergin, the navigator: a medieval odyssey, vigil, vincent ward, what dreams may come movie


Researchers from the Wellcome Sanger Institute, Max Delbrück Center for Molecular Medicine (MDC), Germany, Harvard Medical School, Imperial College London and their global collaborators analysed almost half a million individual cells to build a first extensive draft cell atlas of the human heart. The atlas shows the huge diversity of cells and reveals heart muscle cell types, cardiac protective immune cells, and the intricate network of blood vessels. It also predicts how the cells communicate to keep the heart working.


Published today in Nature (24 September), this study is part of the Human Cell Atlas initiative to map every cell type in the human body. The new molecular and cellular knowledge of the heart will enable better understanding of heart disease and guide more personalised medicine. It could also potentially lead to regenerative medicine in the future.


The quantitative landscape of the human heart proteome. a Experimental design, including the source of material (upper panel), in-depth vs. single-run analyses (middle panel), and schematic depiction of the analytical workflow (lower panel). b Graphical illustration of the human heart showing the total number of quantified proteins in each region. c Quantified proteins in three cardiac cell types and adipose fibroblasts. d Bar plot of the total number of quantified proteins in all heart regions, cell types, and the entire data set