Abstract:
:Functional cardiomyocytes can now be derived routinely from hPSCs (human pluripotent stem cells), which collectively include embryonic and induced pluripotent stem cells. This technology presents new opportunities to develop pharmacologically relevant in vitro screens to detect cardiotoxicity, with a view to improving patient safety while reducing the economic burden to industry arising from high drug attrition rates. In the present article, we consider the need for human cardiomyocytes in drug-screening campaigns and review the strategies used to differentiate hPSCs towards the cardiac lineage. During early stages of differentiation, hPSC-cardiomyocytes display gene expression profiles, ultra-structures, ion channel functionality and pharmacological responses reminiscent of an embryonic phenotype, but maturation during extended time in culture has been demonstrated convincingly. Notably, hPSC-cardiomyocytes have been shown to respond in a highly predictable manner to over 40 compounds that have a known pharmacological effect on the human heart. This suggests that further development and validation of the hPSC-cardiomyocyte model as a tool for assessing cardiotoxicity is warranted.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Dick E,Rajamohan D,Ronksley J,Denning Cdoi
10.1042/BST0381037subject
Has Abstractpub_date
2010-08-01 00:00:00pages
1037-45issue
4eissn
0300-5127issn
1470-8752pii
BST0381037journal_volume
38pub_type
杂志文章,评审abstract::The study of regulated exocytosis uniquely allows the direct measurement of intracellular membrane fusion events in real time. We have exploited this to examine factors that regulate not only the extent but also the dynamics of single fusion/release events. The general strategy used has been to assess exocytosis in tr...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0290467
更新日期:2001-08-01 00:00:00
abstract::Disrupted in schizophrenia 1 (DISC1) is emerging in the eyes of many as the most promising candidate of all the schizophrenia risk genes. This viewpoint is derived from the combination of genetic, clinical, imaging and rapidly advancing cell biology data around this gene. All of these areas have been reviewed extensiv...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0351283
更新日期:2007-11-01 00:00:00
abstract::Tandem repeats (TR) in proteins are common in nature and have several unique functions. They come in various forms that are frequently difficult to recognize from a sequence. A previously proposed structural classification has been recently implemented in the RepeatsDB database. This defines five main classes, mainly ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150079
更新日期:2015-10-01 00:00:00
abstract::Phagocytosis and phagosome maturation are crucial processes in biology. Phagocytosis and the subsequent digestion of phagocytosed particles occur across a huge diversity of eukaryotes and can be achieved by many different cells within one organism. In parallel, diverse groups of pathogens have evolved mechanisms to av...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20130014
更新日期:2013-04-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized countries. NAFLD develops in the absence of alcohol abuse and encompasses a wide spectrum of disorders ranging from benign fatty liver to non-alcoholic steatohepatitis (NASH). NASH often leads to fibrosis, cirrhosis a...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140138
更新日期:2014-10-01 00:00:00
abstract::Phosphoinositide 3-kinases (PI3Ks) are important signalling enzymes in most cell types. Recent gene targeting studies have shed light on the importance of this family of lipid kinases in the immune system, and the complex mechanisms by which these kinases are regulated in vivo. We have recently reported a phenotype of...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0310270
更新日期:2003-02-01 00:00:00
abstract::CoA (coenzyme A) and its derivatives have a critical role in regulating cardiac energy metabolism. This includes a key role as a substrate and product in the energy metabolic pathways, as well as serving as an allosteric regulator of cardiac energy metabolism. In addition, the CoA ester malonyl-CoA has an important ro...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140094
更新日期:2014-08-01 00:00:00
abstract::RNase A (1 mM) was incubated with glucose (0.4 M) at 37 degrees C for up to 14 days in phosphate buffer (0.2 M, pH 7.4), digested with trypsin and analysed by LC-MS. The major sites of fructoselysine formation were Lys(1), Lys(7), Lys(37) and Lys(41). Three of these sites (Lys(7), Lys(37) and Lys(41)) were also the ma...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/bst0311426
更新日期:2003-12-01 00:00:00
abstract::The physiological roles of insulin and insulin-like growth factors (IGFs) are distinct, with insulin acting to regulate cellular uptake and metabolism of fuels, whereas IGFs promote cell growth, survival and differentiation. The only components of signalling pathways known to be unique to insulin and IGFs are their re...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0290513
更新日期:2001-08-01 00:00:00
abstract::Glycogen synthase kinase-3 is an unusual protein serine/threonine kinase that, unlike most of its 500-odd relatives in the genome, is active under resting conditions and is inactivated upon cell stimulation. The two mammalian isoforms, GSK-3alpha and beta, play largely overlapping roles and have been implicated in a v...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0320803
更新日期:2004-11-01 00:00:00
abstract::The mitotic spindle is the macromolecular machine utilized to accurately segregate chromosomes in cells. How this self-organized structure assembles is a key aspect of understanding spindle morphogenesis. In the present review, we focus on understanding mechanisms of spindle self-assembly and address how subcellular s...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140243
更新日期:2015-02-01 00:00:00
abstract::The majority of mRNAs in eukaryotic cells are translated via a method that is dependent upon the recognition of, and binding to, the methylguanosine cap at the 5' end of the mRNA, by a set of protein factors termed eIFs (eukaryotic initiation factors). However, many of the eIFs involved in this process are modified an...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0381581
更新日期:2010-12-01 00:00:00
abstract::There are eight members of the phosphoinositide family of phospholipids in eukaryotes; PI, PI3P, PI4P, PI5P, PI(4,5)P2, PI(3,4)P2, PI(3,5)P2 and PI(3,4,5)P3. Receptor activation of Class I PI3Ks stimulates the phosphorylation of PI(4,5)P2 to form PI(3,4,5)P3. PI(3,4,5)P3 is an important messenger molecule that is part...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20150248
更新日期:2016-02-01 00:00:00
abstract::Sensing and signalling events that detect abiotic stress-induced changes in plant water status and initiate downstream stress responses such as ABA (abscisic acid) accumulation and osmoregulation remain uncharacterized in plants. Although conclusive results are lacking, recent results from plants, and analogies to sig...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0330375
更新日期:2005-04-01 00:00:00
abstract::Plant chloroplasts contain an intricate photosynthetic membrane system, the thylakoids, and are surrounded by two envelope membranes at which thylakoid lipids are assembled. The glycoglycerolipids mono- and digalactosyldiacylglycerol, and sulfoquinovosyldiacylglycerol as well as phosphatidylglycerol, are present in th...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20110752
更新日期:2012-04-01 00:00:00
abstract::Colorectal cancer is the third most common cancer in developed countries such as the U.K., but incidence rates around the world vary approx. 20-fold. Diet is thought to be a key factor determining risk: red and processed meat, but not white meat or fish, are associated with an increased risk of colorectal cancer. The ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0351355
更新日期:2007-11-01 00:00:00
abstract::An RNA world has been placed centre stage for explaining the origin of life. Indeed, RNA is the most plausible molecule able to form both a (self)-replicator and to inherit information, necessities for initiating genetics. However, in parallel with self-replication, the proto-organism had to obtain the ability to cata...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20140132
更新日期:2014-08-01 00:00:00
abstract::In nearly all somatic cells, the ribosome biosynthesis is a key activity. The same is true also for mammalian oocytes and early embryos. This activity is intimately linked to the most prominent nuclear organelles - the nucleoli. Interestingly, during a short period around fertilization, the nucleoli in oocytes and emb...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20190847
更新日期:2020-04-29 00:00:00
abstract::Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cros...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20190312
更新日期:2020-04-29 00:00:00
abstract::Cyclin A must be degraded at prometaphase in order to allow mitosis progression. Nevertheless, the signals that trigger cyclin A degradation at mitosis have been largely elusive. In the present paper, we review the status of cyclin A degradation in the light of recent evidence indicating that acetylation plays a role ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0380083
更新日期:2010-02-01 00:00:00
abstract::The driving force of the cell cycle is the activities of cyclin-dependent kinases (CDKs). Key steps in the regulation of the cell cycle therefore must impinge upon the activities of the CDKs. CDKs exert their functions when bound to cyclins that are expressed cyclically during the cell cycle. Polyamine biosynthesis va...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0310366
更新日期:2003-04-01 00:00:00
abstract::The transcript is populated with numerous overlapping codes that regulate all steps of gene expression. Deciphering these codes is very challenging due to the large number of variables involved, the non-modular nature of the codes, biases and limitations in current experimental approaches, our limited knowledge in gen...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20191048
更新日期:2020-08-28 00:00:00
abstract::We have shown that yeast mutants with defects in the Ada adaptor proteins are defective in hormone-dependent gene activation by ectopically expressed human glucocorticoid receptor (GR). Others have shown that the Ada2 protein is required for physical interactions between some activation domains and TBP (TATA-binding p...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:
更新日期:2000-01-01 00:00:00
abstract::Co-ordinated myocyte handling of calcium is essential for efficient excitation-contraction coupling in the heart. The calcium cycling activity can be modulated by adrenergic stimulation and subsequent phosphorylation. Important functional consequences of phosphorylation include a greater influx of calcium through the ...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0340489
更新日期:2006-08-01 00:00:00
abstract::Native disulphide bonds are essential for the structure and function of many membrane and secretory proteins. Disulphide bonds are formed, reduced and isomerized in the endoplasmic reticulum of mammalian cells by a family of oxidoreductases, which includes protein disulphide isomerase (PDI), ERp57, ERp72, P5 and PDIR....
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0320655
更新日期:2004-11-01 00:00:00
abstract::The most striking example of a complex prokaryotic intracytoplasmic organization can be found in the members of the phylum Planctomycetes. Among them are the anammox (anaerobic ammonium-oxidizing) bacteria, which possess a unique cell compartment with an unprecedented function in bacteria: the anammoxosome is a prokar...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST20110728
更新日期:2011-12-01 00:00:00
abstract::Squalene epoxidase (Erg1p) is an essential enzyme in the ergosterol biosynthesis pathway in yeast. For its enzymatic activity, Erg1p requires molecular oxygen, NAD(P)H and FAD. Amino acid analysis and sequence alignment with other squalene epoxidases revealed two highly conserved FAD-binding domains, FAD I and FAD II....
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST20051197
更新日期:2005-11-01 00:00:00
abstract::Activation of the BCR (B cell antigen receptor) stimulates the production of both PtdIns(3,4,5) P3 and Ins(1,4,5) P3. PtdIns(3,4,5) P3 and Ins(1,4,5) P3 are generated from a common substrate, PtdIns(4,5) P2. In some systems, continuous PtdIns(4,5) P2 synthesis is necessary for maximal Ins(1,4,5) P3 production, but whe...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/bst0320326
更新日期:2004-04-01 00:00:00
abstract::Recent findings that some 24 inherited diseases and anomalies are caused by defects in proteins of the NE (nuclear envelope) and lamina have resulted in a fundamental reassessment of the functions of the NE and underlying lamina. Instead of just regarding the NE and lamina as a molecular filtering device, regulating t...
journal_title:Biochemical Society transactions
pub_type: 杂志文章,评审
doi:10.1042/BST0361329
更新日期:2008-12-01 00:00:00
abstract::Within the SulfoSYS (Sulfolobus Systems Biology) project, the effect of temperature on a metabolic network is investigated at the systems level. Sulfolobus solfataricus utilizes an unusual branched ED (Entner-Doudoroff) pathway for sugar degradation that is promiscuous for glucose and galactose. In the course of metab...
journal_title:Biochemical Society transactions
pub_type: 杂志文章
doi:10.1042/BST0390077
更新日期:2011-01-01 00:00:00