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  • regulation
  • In this thesis it is shown that by casting specific questions on the regulation and control of cell cycle transition points in the here extended framework of MCA, it is possible to derive consensus answers for subsets of mathematical models. (sun.ac.za)
  • ABSTRACT: We propose a protein interaction network for the regulation of DNA synthesis and mitosis that emphasizes the universality of the regulatory system among eukaryotic cells. (cellml.org)
  • The idiosyncrasies of cell cycle regulation in particular organisms can be attributed, we claim, to speci?c settings of rate constants in the dynamic network of chemical reactions. (cellml.org)
  • To support these claims, we convert the reaction mechanism into a set of governing kinetic equations and provide parameter values (specific to budding yeast, fission yeast, frog eggs, and mammalian cells) that account for many curious features of cell cycle regulation in these organisms. (cellml.org)
  • Our approach provides a theoretical framework in which to understand both the universality and particularity of cell cycle regulation, and to construct, in modular fashion, increasingly complex models of the networks controlling cell growth and division. (cellml.org)
  • The precise inheritance of genetic material in eukaryotes requires that initiation at each of the hundreds to thousands of replication origins be subject to exquisite regulation so that the DNA is duplicated exactly once per cell cycle. (grantome.com)
  • Specifically, we are interested in questions such as (i) what are the intracellular fluxes, (ii) what are the regulation mechanisms that a cell uses to control its metabolic fluxes, (iii) what are the principles underlying metabolism. (rug.nl)
  • In the last years, for example, we uncovered - first by computational predictions and later validated by experiments - that cells have mechanisms in place that sense metabolic flux and that are used for flux-dependent regulation. (rug.nl)
  • Gene regulation gives the cell control over structure and function, and is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism. (wikipedia.org)
  • Gene regulation may also serve as a substrate for evolutionary change, since control of the timing, location, and amount of gene expression can have a profound effect on the functions (actions) of the gene in a cell or in a multicellular organism. (wikipedia.org)
  • His research involves problems in cell and developmental biology, such as the dynamics and function of the cytoskeleton, the regulation of the cell cycle, and the process of signaling in embryos, as well as the evolution of the vertebrate body plan, and applying mathematical approaches to biology. (wikipedia.org)
  • The main mechanism of action of the cell cycle checkpoints is through the regulation of the activities of a family of protein kinases known as the cyclin-dependent kinases (CDKs), which bind to different classes of regulator proteins known as cyclins, with specific cyclin-CDK complexes being formed and activated at different phases of the cell cycle. (wikipedia.org)
  • nuclei
  • However, this theory is controversial, and additional experimentation involving archaeal viruses is necessary, as they are probably the most evolutionarily similar to modern eukaryotic nuclei. (wikipedia.org)
  • Bacteria
  • Symbiosis between legumes and Rhizobium bacteria leads to the formation of root nodules where bacteria in the infected plant cells are converted into nitrogen-fixing bacteroids. (pnas.org)
  • In contrast, bacteroids in determinate nodules of the nongalegoid legumes lotus and bean are comparable to free-living bacteria in their genomic DNA content, cell size, and viability. (pnas.org)
  • The bacteria within the nodule cells gain the ability to fix nitrogen gas by means of their nitrogenase enzyme complex and supply the host plant with the reduced nitrogen for plant growth. (pnas.org)
  • Components of the citric acid cycle were derived from anaerobic bacteria, and the TCA cycle itself may have evolved more than once. (wikipedia.org)
  • organisms
  • The citric acid cycle (CAC) - also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle - is a series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins into carbon dioxide and chemical energy in the form of adenosine triphosphate (ATP). (wikipedia.org)
  • All living organisms are products of repeated rounds of cell growth and division. (wikipedia.org)
  • Two research groups have produced several models of the cell cycle simulating several organisms. (wikipedia.org)
  • Biology
  • Marc W. Kirschner (born February 28, 1945) is an American cell biologist and biochemist and the founding chair of the Department of Systems Biology at Harvard Medical School. (wikipedia.org)
  • In 1993, he moved to Harvard Medical School, where he served as the chair of the new Department of Cell Biology for a decade. (wikipedia.org)
  • proliferation
  • Trichostatin A (TSA), isolated as a potent inducer of differentiation in murine erythroleukemia cells, caused reversible arrest of rat 3Y1 fibroblast proliferation in G1 and G2 phases without any inhibition of macromolecular synthesis. (springer.com)
  • Gelfant, S (1977) 'A new concept of tissue and tumor cell proliferation', Cancer Res. (springer.com)
  • It is hypothesized that the modern cell cycle, whereby mitosis, meiosis, and sex occur in all eukaryotes, evolved because of the balances struck by viruses, which characteristically follow a pattern of tradeoff between infecting as many hosts as possible and killing an individual host through viral proliferation. (wikipedia.org)
  • Nucleus
  • Viral eukaryogenesis is the hypothesis that the cell nucleus of eukaryotic life forms evolved from a large DNA virus in a form of endosymbiosis within a methanogenic archaeon. (wikipedia.org)
  • Further, the viral origins of the modern eukaryotic nucleus may have relied on multiple infections of archaeal cells carrying bacterial mitochondrial precursors with lysogenic viruses. (wikipedia.org)
  • The viral eukaryogenesis hypothesis depicts a model of eukaryotic evolution in which a virus, similar to a modern pox virus, evolved into a nucleus via gene acquisition from existing bacterial and archaeal species. (wikipedia.org)
  • control
  • The central question of this thesis focuses on quantifying the control in mathematical models of the G1/S transition by the individual cell cycle processes. (sun.ac.za)
  • The most important extension made it possible to follow and quantify, during a single cell cycle, the control properties of the individual system processes. (sun.ac.za)
  • Subsequently, these newly developed methods were used to determine the control by the individual processes of an important checkpoint in mammalian cells, the restriction point. (sun.ac.za)
  • Here is how the generic cell cycle control model looks like in the Model Builder. (vt.edu)
  • p34Cdc2 kinase family members are known to be essential for eukaryotic cell cycle control. (wikipedia.org)
  • Kirschner studies how cells divide, how they generate their shape, how they control their size, and how embryos develop. (wikipedia.org)
  • His lab is now a leader in using mathematical tools to analyze signaling pathways, cell size control, and the selectivity of drugs. (wikipedia.org)
  • Cell cycle checkpoints are control mechanisms in eukaryotic cells which ensure proper division of the cell. (wikipedia.org)
  • He was awarded the 2001 Nobel Prize in Physiology or Medicine with Paul Nurse and Leland H. Hartwell for their discoveries of protein molecules that control the division of cells. (wikipedia.org)
  • Within the cell cycle, there is a stringent set of regulations known as the cell cycle control system that controls the timing and coordination of the phases to ensure a correct order of events. (wikipedia.org)
  • gene expression
  • In this hands-on activity students review the steps of eukaryotic gene expression and learn how this knowledge can be used to treat genetic disease. (hhmi.org)
  • Cellular Gene Expression Survey of PseudoRabies Virus (PRV) Infection of Human Embryonic Kidney Cells (HEK-293) , Veterinary Research. (irisa.fr)
  • meiosis
  • Meiosis is important to eukaryotes, such as plants, animals and fungi, because it is the method by which they produce sex cells. (reference.com)
  • The viral eukaryogenesis hypothesis points to the cell cycle of eukaryotes, particularly sex and meiosis, as evidence. (wikipedia.org)
  • Synthesis
  • DNA polymerases isolated from cells and artificial DNA primers can be used to initiate DNA synthesis at known sequences in a template DNA molecule. (wikipedia.org)
  • His PhD was supervised by Asher Korner and focused on haemoglobin synthesis in intact rabbit reticulocytes (immature red blood cells), and was awarded in 1968. (wikipedia.org)
  • The location provided a ready supply of surf clams and sea urchins amongst the reefs and fishing docks, and it was these invertebrates that were particularly useful for the study of the synthesis of proteins in embryogenesis, as the embryos were simply generated with the application of filtered sea water, and the transparency of the embryo cells was well suited to microscopic study. (wikipedia.org)
  • During G1 phase, the cell grows in size and synthesizes mRNA and proteins (Known as histones) that are required for DNA synthesis. (wikipedia.org)
  • In order for the cell to continue through the G1-pm, there must be a high amount of growth factors and a steady rate of protein synthesis, otherwise the cell will move into G0 phase. (wikipedia.org)
  • eukaryotes
  • This finding reveals a positive correlation in prokaryotes between DNA content and cell size, similar to that in eukaryotes. (pnas.org)
  • In the original paper it was also an RNA cell at the origin of eukaryotes, but eventually more complex, featuring RNA processing. (wikipedia.org)
  • mutations
  • This interactive focuses on the roles of germline and somatic cell mutations in human disease. (hhmi.org)
  • Interphase
  • Interphase ensures that the cell is the right size and has everything it needs to go through mitosis. (glogster.com)
  • Hunt found that cyclins begin to be synthesised after the eggs are fertilised and increase in levels during interphase, until they drop very quickly in the middle of mitosis in each cell division. (wikipedia.org)
  • In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. (wikipedia.org)
  • G1 phase ends when the cell moves into the S phase of interphase. (wikipedia.org)
  • G1 phase together with the S phase and G2 phase comprise the long growth period of the cell cycle called interphase that takes place before cell division in mitosis (M phase). (wikipedia.org)
  • checkpoints
  • The transition between these phases is regulated by so-called checkpoints, which are important to ensure proper functioning of the cell cycle. (sun.ac.za)
  • Explore the phases, checkpoints, and protein regulators of the cell cycle in this highly interactive Click and Learn and find out how mutated versions of these proteins can lead to the development of cancer. (hhmi.org)
  • progression of the cell
  • Some authors will say that the restriction point and the G1/S checkpoint are one and the same, but more recent studies have argued that there are two different points in the G1 phase that check the progression of the cell. (wikipedia.org)
  • transition
  • On the other hand, staurosporine, which we rediscovered as a new inhibitor of the cell cycle blocking Gl and G2, induced synchronous G2/M transition after release from the G2 arrest. (springer.com)
  • Such a checkpoint ensures that cells would have a critical mass at the G1/S transition point. (sun.ac.za)
  • induce cell
  • Nod factors induce cell divisions in the root cortex and successive divisions lead to the formation of the nodule primordium. (pnas.org)
  • Other mechanisms may include the activity of HDIs to induce cell differentiation, thus acting to "mature" some of the de-differentiated cells found in tumors. (wikipedia.org)
  • arrest
  • Cells released from the G2-arrest by both drugs entered a new S phase without passage through M phase, resulting in the formation of proliferative tetraploid cells. (springer.com)
  • species
  • The evolution of sexual reproduction describes how sexually reproducing animals, plants, fungi and protists evolved from a common ancestor that was a single celled eukaryotic species. (wikipedia.org)
  • model
  • This CellML model represents the mammalian cell model taken from the original model code. (cellml.org)
  • In studies at UC San Francisco of the frog embryo as a model system of cell development, Kirschner identified the first inducer of embryonic differentiation, fibroblast growth factor (FGF), an early finding in the field of signal transduction. (wikipedia.org)
  • The complex network of biochemical reaction/transport processes and their spatial organization make the development of a predictive model of a living cell a grand challenge for the 21st century. (wikipedia.org)
  • this type of model is called a deterministic process (whereas a model describing a statistical distribution of protein concentrations in a population of cells is called a stochastic process). (wikipedia.org)
  • interactions
  • The importance of proteolytic degradation in eukaryotic cell cycle changed the view of cell division as a simple kinase cascade to a more complex process in which interactions among phosphorylation, ubiquitination, and proteolysis are necessary. (wikipedia.org)
  • bacterial cell
  • Plant factors present in nodules of galegoid legumes but absent from nodules of nongalegoid legumes block bacterial cell division and trigger endoreduplication cycles, thereby forcing the endosymbionts toward a terminally differentiated state. (pnas.org)
  • and another prokaryotic (bacterial) cell that, by endocytosis, became the modern mitochondrion or chloroplast. (wikipedia.org)
  • Oxidative Phosphorylation
  • The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. (wikipedia.org)
  • The NADH and FADH2 generated by the citric acid cycle are, in turn, used by the oxidative phosphorylation pathway to generate energy-rich ATP. (wikipedia.org)
  • restriction point
  • The G1 checkpoint, also known as the restriction point in mammalian cells and the start point in yeast, is the point at which the cell becomes committed to entering the cell cycle. (wikipedia.org)
  • As the cell progresses through G1, depending on internal and external conditions, it can either delay G1, enter a quiescent state known as G0, or proceed past the restriction point. (wikipedia.org)
  • The restriction point (R) in the G1 phase is different from a checkpoint because it does not determine whether cell conditions are ideal to move on to the next phase, but it changes the course of the cell. (wikipedia.org)
  • After a vertebrate cell has been in the G1 phase for about three hours, the cell enters a restriction point in which it is decided whether the cell will move forward with the G1 phase or move into the dormant G0 phase. (wikipedia.org)
  • The first restriction point is growth-factor dependent and determines whether the cell moves into the G0 phase, while the second checkpoint is nutritionally-dependent and determines whether the cell moves into the S phase. (wikipedia.org)
  • dynamical
  • Traditionally, models for biological systems that show rich dynamic behavior, such as the cell cycle, are studied using dynamical systems analysis. (sun.ac.za)
  • Cell Collective is a modeling software that enables one to house dynamical biological data, build computational models, stimulate, break and recreate models. (wikipedia.org)
  • Cellular
  • Cellular respiration, with a series of steps and intracellular functions, is the method used by cells to release energy from chemical bonds of molecules, s. (reference.com)
  • differentiation
  • Here we demonstrate that differentiation of bacteroids in indeterminate nodules of Medicago and related legumes from the galegoid clade shows remarkable similarity to host cell differentiation. (pnas.org)
  • These postmitotic cells are unable to divide and enter the nodule differentiation program. (pnas.org)
  • division
  • ENGLISH ABSTRACT: The multiplication of cells proceeds through consecutive phases of growth and division (G1, S, G2 and M phases), in a process known as the cell cycle. (sun.ac.za)
  • This may be because of the cell division event which we are currently unable to express in CellML. (cellml.org)
  • In the case of determinate nodules, the initial cell division activity required for nodule primordium formation ceases rapidly and therefore the determinate nodules contain no meristem. (pnas.org)
  • Cyclins are proteins that play a key role in regulating the cell-division cycle. (wikipedia.org)
  • In humans, the normal physiological temperature is around 37 °C (98.6 °F). G1 phase is particularly important in the cell cycle because it determines whether a cell commits to division or to leaving the cell cycle. (wikipedia.org)
  • HeLa
  • Recent evidence (preprinted at BioRxiv) suggests widespread human protein phosphorylation on multiple non-canonical amino acids, including motifs containing phosphorylated histidine, aspartate, glutamate, arginine and lysine in HeLa cell extracts. (wikipedia.org)
  • endocytosis
  • Rhizobia are released from infection threads in the cytoplasm of postmitotic nondividing cells by endocytosis. (pnas.org)
  • Microtubules
  • Nocodazole is an antineoplastic agent which exerts its effect in cells by interfering with the polymerization of microtubules. (wikipedia.org)
  • Microtubules are one type of fibre which constitutes the cytoskeleton, and the dynamic microtubule network has several important roles in the cell, including vesicular transport, forming the mitotic spindle and in cytokinesis. (wikipedia.org)
  • Interestingly, nocodazole has been shown to decrease the oncogenic potential of cancer cells via another microtubules-independent mechanisms. (wikipedia.org)
  • These functional Golgi ministacks remain distributed about the cell, unable to track forward to form a perinuclear Golgi since nocodazole has depolymerized the microtubules. (wikipedia.org)
  • Microtubules are nucleated and organized by microtubule organizing centers (MTOCs), such as the centrosome found in the center of many animal cells or the basal bodies found in cilia and flagella, or the spindle pole bodies found in most fungi. (wikipedia.org)
  • bacteria
  • Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin, with the mtDNA being derived from the circular genomes of the bacteria that were engulfed by the early ancestors of today's eukaryotic cells. (wikipedia.org)
  • germline
  • In Xenopus , the germline is specified through the inheritance of germ plasm formed during oogenesis and asymmetrically segregated into the future germ cell lineage. (biologists.org)
  • life cycles
  • A few genera have life-cycles involving a secondary host, which may be a vertebrate, invertebrate or plant. (wikipedia.org)
  • A variety of different morphological forms appear in the life cycles of trypanosomatids, distinguished mainly by the position, length and the cell body attachment of the flagellum. (wikipedia.org)
  • Epimastigotes are a common form in the insect host and Crithidia and Blastocrithidia, both parasites of insects, exhibit this form during their life cycles. (wikipedia.org)
  • cilia
  • Cilia occur in all members of the group (although the peculiar Suctoria only have them for part of the life-cycle) and are variously used in swimming, crawling, attachment, feeding, and sensation. (wikipedia.org)
  • Histone
  • There are sixteen variants of histone H2B found in humans, thirteen of which are expressed in regular body cells and three of which are only expressed in the testes. (wikipedia.org)
  • histone H2B isoforms can be added to nucleosomes at other times during the cell cycle. (wikipedia.org)
  • biology
  • In the mid-1990s, my research group began to devise a method to establish endothelial cell cultures from human peripheral blood, with an ultimate goal of examining interindividual heterogeneity of endothelial biology. (jci.org)
  • As nocodazole affects the cytoskeleton, it is often used in cell biology experiments as a control: for example, some dominant negative Rho small GTPases cause a similar effect as nocodazole, and constitutively activated mutants often reverse or negate the effect. (wikipedia.org)
  • Nocodazole is frequently used in cell biology laboratories to synchronize the cell division cycle. (wikipedia.org)
  • fungi
  • When nutrients are scarce, myxobacterial cells aggregate into fruiting bodies (not to be confused with those in fungi), a process long-thought to be mediated by chemotaxis but now considered to be a function of a form of contact-mediated signaling. (wikipedia.org)
  • In fungi, the sexual fusion of haploid cells is called karyogamy. (wikipedia.org)
  • Although fungi are eukaryotic, many pathogenic fungi are microorganisms. (wikipedia.org)
  • humans
  • In humans, the normal physiological temperature is around 37 °C (98.6 °F). G1 phase is particularly important in the cell cycle because it determines whether a cell commits to division or to leaving the cell cycle. (wikipedia.org)
  • Cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae), also known as CDC73 and parafibromin, is a protein which in humans is encoded by the CDC73 gene. (wikipedia.org)
  • phenotypes
  • These phenotypes were unexpectedly linked to mutations in the gene encoding a subunit of the Go-Ichi-Ni-San (GINS) complex, which is essential for DNA replication prior to cell division. (jci.org)
  • macrophages
  • Natural killer (NK) T-cells and macrophages are also closely associated with the progression of liver injury caused by ConA [ 5 ]. (hindawi.com)
  • Infecting C. neoformans cells are usually phagocytosed by alveolar macrophages in the lung. (wikipedia.org)
  • The invading C. neoformans cells may be killed by the release of oxidative and nitrosative molecules by these macrophages. (wikipedia.org)
  • However some C. neoformans cells may survive within the macrophages. (wikipedia.org)
  • Studies have shown that hosts with higher levels of immune response cells such as monocytes/macrophages, dendritic cells, and invariant natural killer (iNK) T-cells exhibited greater control of fungal growth and protection against systemic infection. (wikipedia.org)
  • immune
  • Concanavalin A (ConA) has the ability to stimulate the activation of T lymphocytes, mostly CD4 + T-cells, leading to immune hepatitis in mice [ 3 , 4 ]. (hindawi.com)
  • Together, the results of this study lay the groundwork for future studies to explore the role of DNA replication in immune cell generation and function. (jci.org)
  • concentration
  • Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. (wikipedia.org)
  • For cell synchronization experiments, nocodazole is usually used at a concentration of 40-100 ng/mL of culture medium for a duration of 12-18 hours. (wikipedia.org)
  • processes
  • Tubulin and microtubule-mediated processes, like cell locomotion, were seen by early microscopists, like Leeuwenhoek (1677). (wikipedia.org)
  • Through the processes of compaction, cell division, and blastulation, the conceptus takes the form of the blastocyst by the fifth day of development, just as it approaches the site of implantation. (wikipedia.org)
  • vertebrate
  • After a vertebrate cell has been in the G1 phase for about three hours, the cell enters a restriction point in which it is decided whether the cell will move forward with the G1 phase or move into the dormant G0 phase. (wikipedia.org)
  • This heteroxenous life cycle typically includes the intestine of a bloodsucking insect and the blood and/or tissues of a vertebrate. (wikipedia.org)
  • deficient
  • Further characterization revealed that these patients were neutropenic and NK cell deficient. (jci.org)
  • structure
  • They are involved in maintaining the structure of the cell and, together with microfilaments and intermediate filaments, they form the cytoskeleton. (wikipedia.org)
  • Typically
  • They typically travel in swarms (also known as wolf packs), containing many cells kept together by intercellular molecular signals. (wikipedia.org)
  • undergoes
  • Within the citric acid cycle, isocitrate, produced from the isomerization of citrate, undergoes both oxidation and decarboxylation. (wikipedia.org)
  • known
  • We tested the EF-1 alpha version in Jurkat cells, a cell line known to show reduced expression and clonal variation in expression from CMV-based vectors. (clontech.com)
  • The cleaved RNAs are then loaded onto a Piwi family protein to aid in the cleavage of complementary based RNA, a reaction known as the "ping-pong cycle. (biomedcentral.com)
  • The phage gene and insert DNA hybrid is then inserted (a process known as "transduction") into Escherichia coli (E. coli) bacterial cells such as TG1, SS320, ER2738, or XL1-Blue E. coli. (wikipedia.org)
  • After R and before S, the cell is known as being in G1-ps, or the pre S phase interval of the G1 phase. (wikipedia.org)
  • For example, the amastigote (prefix "a-", meaning no flagellum) form is also known as the leishmanial form as all Leishmania have an amastigote life cycle stage. (wikipedia.org)
  • determines
  • A proper balance between Bcl-2 and Bax determines cell survival and cell death. (hindawi.com)
  • The first restriction point is growth-factor dependent and determines whether the cell moves into the G0 phase, while the second checkpoint is nutritionally-dependent and determines whether the cell moves into the S phase. (wikipedia.org)
  • organism
  • Applications of phage display technology include determination of interaction partners of a protein (which would be used as the immobilised phage "bait" with a DNA library consisting of all coding sequences of a cell, tissue or organism) so that the function or the mechanism of the function of that protein may be determined. (wikipedia.org)
  • progression
  • Some authors will say that the restriction point and the G1/S checkpoint are one and the same, but more recent studies have argued that there are two different points in the G1 phase that check the progression of the cell. (wikipedia.org)
  • The G1/S checkpoint is the point between G1 phase and the S phase in which the cell is cleared for progression into the S phase. (wikipedia.org)
  • dependent
  • Therefore, ConA-induced hepatitis is an ideal model to investigate the mechanisms and treatments of T-cell-dependent hepatotoxicity. (hindawi.com)
  • Antagonizes MYC transcriptional activity by competing for MAX and suppresses MYC dependent cell transformation. (uniprot.org)
  • important
  • In the case of mucosal candidiasis, the cells that produce cytokine IL-17 are extremely important in maintaining innate immunity. (wikipedia.org)
  • sperm
  • In seedless plants, the archegonium is usually flask-shaped, with a long hollow neck through which the sperm cell enters. (wikipedia.org)
  • In human fertilization, a released ovum (a haploid secondary oocyte with replicate chromosome copies) and a haploid sperm cell (male gamete)-combine to form a single 2n diploid cell called the zygote. (wikipedia.org)
  • mechanisms
  • The reaction is stimulated by the simple mechanisms of substrate availability (isocitrate, NAD+ or NADP+, Mg2+ / Mn2+ ), product inhibition (by NADH (or NADPH outside the citric acid cycle) and alpha-ketoglutarate), and competitive feedback inhibition (by ATP). (wikipedia.org)
  • human
  • The EF-1 alpha promoter in these systems is derived from the human EEF1A1 gene that expresses the alpha subunit of eukaryotic elongation factor 1. (clontech.com)
  • also grew simple human cells in a dish that were designed to react specifically to the bad forms of tau. (elifesciences.org)