BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Adult Cardiac Stem Cells Are Multipotent and Support Myocardial Regeneration

It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.

/pdf/evidence-for-cardiomyocyte-renewal-in-humans-a5djz8s7ml.pdf

Evidence for cardiomyocyte renewal in humans

Attempts to repair myocardial infarcts by transplanting cardiomyocytes or skeletal myoblasts have failed to reconstitute healthy myocardium and coronary vessels integrated structurally and functionally with the remaining viable portion of the ventricular wall. The recently discovered growth and transdifferentiation potential of primitive bone marrow cells (BMC) prompted us, in an earlier study, to inject in the border zone of acute infarcts Lin− c-kitPOS BMC from syngeneic animals. These BMC differentiated into myocytes and vascular structures, ameliorating the function of the infarcted heart. Two critical determinants seem to be required for the transdifferentiation of primitive BMC: tissue damage and a high level of pluripotent cells. On this basis, we hypothesized here that BMC, mobilized by stem cell factor and granulocyte-colony stimulating factor, would home to the infarcted region, replicate, differentiate, and ultimately promote myocardial repair. We report that, in the presence of an acute myocardial infarct, cytokine-mediated translocation of BMC resulted in a significant degree of tissue regeneration 27 days later. Cytokine-induced cardiac repair decreased mortality by 68%, infarct size by 40%, cavitary dilation by 26%, and diastolic stress by 70%. Ejection fraction progressively increased and hemodynamics significantly improved as a consequence of the formation of 15 × 106 new myocytes with arterioles and capillaries connected with the circulation of the unaffected ventricle. In conclusion, mobilization of primitive BMC by cytokines might offer a noninvasive therapeutic strategy for the regeneration of the myocardium lost as a result of ischemic heart disease and, perhaps, other forms of cardiac pathology.

https://www.pnas.org/content/pnas/98/18/10344.full.pdf

Mobilized bone marrow cells repair the infarcted heart, improving function and survival

Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes and vascular cells, either by transdifferentiation or cell fusion, appear too low to explain the significant cardiac improvement described. Accordingly, we and others have advanced an alternative hypothesis: the transplanted stem cells release soluble factors that, acting in a paracrine fashion, contribute to cardiac repair and regeneration. Indeed, cytokines and growth factors can induce cytoprotection and neovascularization. It has also been postulated that paracrine factors may mediate endogenous regeneration via activation of resident cardiac stem cells. Furthermore, cardiac remodeling, contractility, and metabolism may also be influenced in a paracrine fashion. This article reviews the potential paracrine mechanisms involved in adult stem cell signaling and therapy.

Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy

Background The scarring of the heart that results from myocardial infarction has been interpreted as evidence that the heart is composed of myocytes that are unable to divide. However, recent observations have provided evidence of proliferation of myocytes in the adult heart. Therefore, we studied the extent of mitosis among myocytes after myocardial infarction in humans. Methods Samples from the border of the infarct and from areas of the myocardium distant from the infarct were obtained from 13 patients who had died 4 to 12 days after infarction. Ten normal hearts were used as controls. Myocytes that had entered the cell cycle in preparation for cell division were measured by labeling of the nuclear antigen Ki-67, which is associated with cell division. The fraction of myocyte nuclei that were undergoing mitosis was determined, and the mitotic index (the ratio of the number of nuclei undergoing mitosis to the number not undergoing mitosis) was calculated. The presence of mitotic spindles, contractile ri...

https://www.nejm.org/doi/pdf/10.1056/NEJM200110113451516

Evidence That Human Cardiac Myocytes Divide after Myocardial Infarction

It is no doubt that the evolutionary process is affected by chance, but the question is to what extent the chance plays its role. The random analysis can throw light on the underlying reasoning for the primary structure of proteins. With the use of random principles, we have explored three approaches to analyse protein primary structure, i.e. the randomness in the construction of amino-acid sequences, in the follow-up amino acid, and in the distribution of amino acid/amino acids. As the results, (i) we can evaluate the impact of chance on the composition of aminoacid sequences by comparing the measured probability/frequency with the predicted probability/ frequency; (ii) we can evaluate the impact of chance on the follow-up amino acid by comparing the Markov transition probability with the predicted conditional probability; and (iii) we can evaluate the effect of chance on the distribution of amino acids by comparing the real distribution probability with the theoretical distribution probability. These approaches can be used to quantitatively analyse the primary structure of intra-protein as well as inter-proteins, thus we can get more insights into the mechanisms of protein construction, mutation, and evolutionary process. Also, these approaches may have some potential use for development of new drugs.

Randomness in the Primary Structure of Protein: Methods and Implications

Cellulase plays an important role in modern industry and holds great potential in biofuel production. Many different types of organisms produce cellulase, which go through secretory pathways to reach the extracellular space, where enzymatic reactions take place. Secretory pathways in various cells have been the focus of many research fields; however, there are few studies on secretory pathways of cellulases in the literature. It is therefore necessary and important to review the current knowledge on the secretory pathways of cellulases. In this mini-review, we address the subcellular locations of cellulases in different organisms, discuss the secretory pathways of cellulases in different organisms, and examine the secretory mechanisms of cellulases. These sections start with a description of general secreted proteins, advance to the situation of cellulases, and end with the knowledge of cellulases, as documented in UniProt Knowledgebase (UniProtKB). Finally, gaps in existing knowledge are highlighted, which may shed light on future studies for biofuel engineering.

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Secretory pathway of cellulase: a mini-review

Although polycyclic aromatic hydrocarbons (PAHs) are harmful to human health, their elimination from the environment is not easy. Biodegradation of PAHs is promising since many bacteria have the ability to use hydrocarbons as their sole carbon and energy sources for growth. Of various microorganisms that can degrade PAHs, Pseudomonas aeruginosa is particularly important, not only because it causes a series of diseases including infection in cystic fibrosis patients, but also because it is a model bacterium in various studies. The genes that are responsible for degrading PAHs have been identified in P. aeruginosa, however, no gene acts alone as various stresses often initiate different metabolic pathways, quorum sensing, biofilm formation, antibiotic tolerance, etc. Therefore, it is important to study how PAH degradation genes behave under different conditions. In this study, we apply network analysis to investigating how 46 PAH degradation genes reorganized among 5549 genes in P. aeruginosa PAO1 under nine different conditions using publicly available gene coexpression data from GEO. The results provide six aspects of novelties: (i) comparing the number of gene clusters before and after stresses, (ii) comparing the membership in each gene cluster before and after stresses, (iii) defining which gene changed its membership together with PAH degradation genes before and after stresses, (iv) classifying membership-changed-genes in terms of category in Pseudomonas Genome Database, (v) postulating unknown gene's function, and (vi) proposing new mechanisms for genes of interests. This study can shed light on understanding of cooperative mechanisms of PAH degradation from the level of entire genes in an organism, and paves the way to conduct the similar studies on other genes.

/pdf/reorganization-of-gene-network-for-degradation-of-polycyclic-7oyi1zrjff.pdf

Reorganization of gene network for degradation of polycyclic aromatic hydrocarbons (PAHs) in Pseudomonas aeruginosa PAO1 under several conditions

SO2 emissions lead to various harmful effects on environment and human health. The SO2 emission in China has significant contribution to the global SO2 emission, so it is necessary to employ various methods to study SO2 emissions in China with great details in order to lay the foundation for policymaking to improve environmental conditions in China. Network analysis is used to analyze the SO2 emissions from power generation, industrial, residential and transportation sectors in China for 2008 and 2010, which are recently available from 1744 ground surface monitoring stations. The results show that the SO2 emissions from power generation sector were highly individualized as small-sized clusters, the SO2 emissions from industrial sector underwent an integration process with a large cluster contained 1674 places covering all industrial areas in China, the SO2 emissions from residential sector was not impacted by time, and the SO2 emissions from transportation sector underwent significant integration. Hierarchical structure is obtained by further combining SO2 emissions from all four sectors and is potentially useful to find out similar patterns of SO2 emissions, which can provide information on understanding the mechanisms of SO2 pollution and on designing different environmental measure to combat SO2 emissions.

/pdf/so-2-emissions-in-china-their-network-and-hierarchical-3jiatfc1hx.pdf

Shaomin Yan

Papers

Evidence That Human Cardiac Myocytes Divide after Myocardial Infarction

Randomness in the Primary Structure of Protein: Methods and Implications

Secretory pathway of cellulase: a mini-review

Reorganization of gene network for degradation of polycyclic aromatic hydrocarbons (PAHs) in Pseudomonas aeruginosa PAO1 under several conditions

SO 2 Emissions in China – Their Network and Hierarchical Structures