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101.
Shaul Druckmann Thomas K. Berger Sean Hill Felix Schürmann Henry Markram Idan Segev 《Biological cybernetics》2008,99(4-5):371-379
Neuron models, in particular conductance-based compartmental models, often have numerous parameters that cannot be directly determined experimentally and must be constrained by an optimization procedure. A common practice in evaluating the utility of such procedures is using a previously developed model to generate surrogate data (e.g., traces of spikes following step current pulses) and then challenging the algorithm to recover the original parameters (e.g., the value of maximal ion channel conductances) that were used to generate the data. In this fashion, the success or failure of the model fitting procedure to find the original parameters can be easily determined. Here we show that some model fitting procedures that provide an excellent fit in the case of such model-to-model comparisons provide ill-balanced results when applied to experimental data. The main reason is that surrogate and experimental data test different aspects of the algorithm’s function. When considering model-generated surrogate data, the algorithm is required to locate a perfect solution that is known to exist. In contrast, when considering experimental target data, there is no guarantee that a perfect solution is part of the search space. In this case, the optimization procedure must rank all imperfect approximations and ultimately select the best approximation. This aspect is not tested at all when considering surrogate data since at least one perfect solution is known to exist (the original parameters) making all approximations unnecessary. Furthermore, we demonstrate that distance functions based on extracting a set of features from the target data (such as time-to-first-spike, spike width, spike frequency, etc.)—rather than using the original data (e.g., the whole spike trace) as the target for fitting—are capable of finding imperfect solutions that are good approximations of the experimental data. 相似文献
102.
Magnesium transport and function in plants: the tip of the iceberg 总被引:19,自引:0,他引:19
Orit Shaul 《Biometals》2002,15(3):307-321
The maintenance of Mg2+ homeostasis in the plant is essential for viability. This review describes Mg2+ functions and balancing in plants, with special focus on the existing knowledge of the involved transport mechanisms. Mg2+ is essential for the function of many cellular enzymes and for the aggregation of ribosomes. Mg2+ concentrations also modulate ionic currents across the chloroplast and the vacuolar membranes, and might thus regulate ion balance in the cell and stomatal opening. The significance of Mg2+ homeostasis has been particularly established with regard to Mg2+'s role in photosynthesis. Mg2+ is the central atom of the chlorophyll molecule, and fluctuations in its levels in the chloroplast regulate the activity of key photosynthetic enzymes. Relatively little is known of the proteins mediating Mg2+ uptake and transport in plants. The plant vacuole seem to play a key role in Mg2+ homeostasis in plant cells. Physiological and molecular evidence indicate that Mg2+ entry to the vacuole is mediated by Mg2+/H+ exchangers. The Arabidopsis vacuolar Mg2+/H+ exchanger, AtMHX, is highly transcribed at the vascular tissue, apparently most abundantly at the xylem parenchyma. Inclusion of Mg2+ ions into the vacuoles of this tissue may determine their partitioning between the various plant organs. Impacts of Mg2+ imbalance are described with respect for both plant physiology and for its nutritional value to animal and human. 相似文献
103.
O Shaul D W Hilgemann J de-Almeida-Engler M Van Montagu D Inz G Galili 《The EMBO journal》1999,18(14):3973-3980
Cellular functions require adequate homeostasis of several divalent metal cations, including Mg(2+) and Zn(2+). Mg(2+), the most abundant free divalent cytoplasmic cation, is essential for many enzymatic reactions, while Zn(2+) is a structural constituent of various enzymes. Multicellular organisms have to balance not only the intake of Mg(2+) and Zn(2+), but also the distribution of these ions to various organs. To date, genes encoding Mg(2+) transport proteins have not been cloned from any multicellular organism. We report here the cloning and characterization of an Arabidopsis thaliana transporter, designated AtMHX, which is localized in the vacuolar membrane and functions as an electrogenic exchanger of protons with Mg(2+) and Zn(2+) ions. Functional homologs of AtMHX have not been cloned from any organism. Ectopic overexpression of AtMHX in transgenic tobacco plants render them sensitive to growth on media containing elevated levels of Mg(2+) or Zn(2+), but does not affect the total amounts of these minerals in shoots of the transgenic plants. AtMHX mRNA is mainly found at the vascular cylinder, and a large proportion of the mRNA is localized in close association with the xylem tracheary elements. This localization suggests that AtMHX may control the partitioning of Mg(2+) and Zn(2+) between the various plant organs. 相似文献
104.
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106.
SuE Yu Svetlan Vassilev Zhong Ri Lim Jaichandran Sivalingam Alan Tin Lun Lam Valerie Ho Laurent Renia Benoit Malleret Shaul Reuveny Steve Kah Weng Oh 《Cell proliferation》2022,55(8)
ObjectivesLarge‐scale generation of universal red blood cells (RBCs) from O‐negative (O‐ve) human induced pluripotent stem cells (hiPSCs) holds the potential to alleviate worldwide shortages of blood and provide a safe and secure year‐round supply. Mature RBCs and reticulocytes, the immature counterparts of RBCs generated during erythropoiesis, could also find important applications in research, for example in malaria parasite infection studies. However, one major challenge is the lack of a high‐density culture platform for large‐scale generation of RBCs in vitro.Materials and MethodsWe generated 10 O‐ve hiPSC clones and evaluated their potential for mesoderm formation and erythroid differentiation. We then used a perfusion bioreactor system to perform studies with high‐density cultures of erythroblasts in vitro.ResultsBased on their tri‐lineage (and specifically mesoderm) differentiation potential, we isolated six hiPSC clones capable of producing functional erythroblasts. Using the best performing clone, we demonstrated the small‐scale generation of high‐density cultures of erythroblasts in a perfusion bioreactor system. After process optimization, we were able to achieve a peak cell density of 34.7 million cells/ml with 92.2% viability in the stirred bioreactor. The cells expressed high levels of erythroblast markers, showed oxygen carrying capacity, and were able to undergo enucleation.ConclusionsThis study demonstrated a scalable platform for the production of functional RBCs from hiPSCs. The perfusion culture platform we describe here could pave the way for large volume‐controlled bioreactor culture for the industrial generation of high cell density erythroblasts and RBCs.Human pluripotent stem cell‐derived red blood cells could help alleviate worldwide blood shortages and provide a secure year‐round supply. However, current generation methods lack the necessary scalability. Here, we present the selection of O‐negative hiPSC clones and demonstrate the small‐scale generation of functional erythroblasts in a high‐density perfusion bioreactor system. 相似文献
107.
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108.
Hagai Karchi Orit Shaul Gad Galili 《The Plant journal : for cell and molecular biology》1993,3(5):721-727
In order to study the regulation of threonine and methionine synthesis in plant seeds, tobacco plants were transformed with a chimeric gene containing the coding DNA sequence of a mutant lysC gene from Escherichia coli fused to a promoter from a phaseolin seed storage protein gene. The bacterial mutant lysC gene codes for aspartate kinase (AK) which is desensitized to feedback inhibition by lysine and threonine. Increased AK activity, compared with control non-transformed plants, was detected in seeds but not in leaves, roots and flowers of the transgenic plants. This expression was accompanied by a significant increase in the levels of free threonine and methionine in the seed. The level of these amino acids also correlated positively with the levels of the bacterial enzyme. No alteration in plant phenotype and 'average seed weight' was observed in any of the transgenic plants, indicating that plant growth and seed development were normal. This study demonstrates, for the first time, that the threonine and methionine biosynthetic pathways are active in plant seeds. Thus, targeting of the production of favorable biosynthetic enzymes to plant seeds may represent a desirable molecular approach for production of crop plants with a more balanced nutritional quality. 相似文献
109.
The enhancers of several distinct viruses contain a common functional element, termed EP. This element binds ubiquitous cellular proteins and generates specific complexes in gel retardation analysis. Ultraviolet cross-linking and Southwestern analysis showed that a 140 kd polypeptide is the major EP DNA-binding protein. Using a combination of DNA binding and immunological techniques, we have identified the c-abl protein in a nuclear complex that binds to the EP element. abl was found to have both a specific and high affinity DNA binding activity. The ability to bind DNA is abolished in the mutant abl protein, p210bcr-abl, consistent with its cytoplasmic localization in chronic myelogenous leukemia. 相似文献
110.
The formation of the lateral distribution of the major antenna complex of photosystem II (LHCIIb) between the granal and stromal lamellae was studied. Specifically, the localization of the insertion and the assembly of the precursor of the apoprotein of LHCIIb (pLHCP) were studied with isolated thylakoids. After insertion of pLHCP into isolated thylakoids, fractionation of the latter into granal and stromal lamellar was performed. At 25 °C most of the precursor was located in the granal lamellae, although both highly purified granal and stromal lamellar fractions demonstrated a similar capability to insert pLHCP. When the insertion reaction to the thylakoids was performed at 10 °C, followed by their separation into stromal and granal lamellae, the labelled pLHCP was localized in the stromal ones. To examine whether pLHCP inserts into both granal and stromal lamellae, or preferentially into stromal lamellae and subsequently migrating to granal lamellae, a chase experiment was performed. Insertion of pLHCP at 10 °C was followed by chase of the radioactive precursor with excess of non-radioactive pLHCP at 25 °C. From the results presented it is evident that the level of pLHCP in stromal lamellae was gradually reduced, while it gradually accumulated in the granal lamellae. Furthermore, the pLHCP in the stromal lamellae was found to be in a free form, while after migrating to the granal lamellae it assembled into the pigmented LHCIIb. 相似文献