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81.
Different autonomous myogenic cell populations revealed by ablation of Myf5-expressing cells during mouse embryogenesis 总被引:2,自引:0,他引:2
Gensch N Borchardt T Schneider A Riethmacher D Braun T 《Development (Cambridge, England)》2008,135(9):1597-1604
The development of myogenic cells is mainly determined by expression of two myogenic factors, Myf5 and Myod1 (MyoD), which genetically compensate for each other during embryogenesis. Here, we demonstrate by conditional cell ablation in mice that Myf5 determines a distinct myogenic cell population, which also contains some Myod1-positive cells. Ablation of this lineage uncovers the presence of a second autonomous myogenic lineage, which superseded Myf5-dependent myogenic cells and expressed Myod1. By contrast, ablation of myogenin-expressing cells erased virtually all differentiated muscle cells, indicating that some aspects of the myogenic program are shared by most skeletal muscle cells. We conclude that Myf5 and Myod1 define different cell lineages with distinct contributions to muscle precursor cells and differentiated myotubes. Individual myogenic cell lineages seem to substitute for each other within the developing embryo. 相似文献
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Long food chains are in general chaotic 总被引:1,自引:0,他引:1
The question whether chaos exists in nature is much debated. In this paper we prove that chaotic parameter regions exist generically in food chains of length greater than three. While nonchaotic dynamics is also possible, the presence of chaotic parameter regions indicates that chaotic dynamics is likely. We show that the chaotic regions survive even at high exponents of closure. Our results have been obtained using a general food chain model that describes a large class of different food chains. The existence of chaos in models of such generality can be deduced from the presence of certain bifurcations of higher codimension. 相似文献
84.
Roger Calixto Behrouz Salamat Thilo Rode Tanja Hartmann Bart Volckaerts Patrick Ruther Thomas Lenarz Hubert H. Lim 《PloS one》2013,8(12)
Ongoing clinical studies on patients recently implanted with the auditory midbrain implant (AMI) into the inferior colliculus (IC) for hearing restoration have shown that these patients do not achieve performance levels comparable to cochlear implant patients. The AMI consists of a single-shank array (20 electrodes) for stimulation along the tonotopic axis of the IC. Recent findings suggest that one major limitation in AMI performance is the inability to sufficiently activate neurons across the three-dimensional (3-D) IC. Unfortunately, there are no currently available 3-D array technologies that can be used for clinical applications. More recently, there has been a new initiative by the European Commission to fund and develop 3-D chronic electrode arrays for science and clinical applications through the NeuroProbes project that can overcome the bulkiness and limited 3-D configurations of currently available array technologies. As part of the NeuroProbes initiative, we investigated whether their new array technology could be potentially used for future AMI patients. Since the NeuroProbes technology had not yet been tested for electrical stimulation in an in vivo animal preparation, we performed experiments in ketamine-anesthetized guinea pigs in which we inserted and stimulated a NeuroProbes array within the IC and recorded the corresponding neural activation within the auditory cortex. We used 2-D arrays for this initial feasibility study since they were already available and were sufficient to access the IC and also demonstrate effective activation of the central auditory system. Based on these encouraging results and the ability to develop customized 3-D arrays with the NeuroProbes technology, we can further investigate different stimulation patterns across the ICC to improve AMI performance. 相似文献
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Elena Ostertag Liujuan Zheng Karina Broger Thilo Stehle Shu-Ming Li Georg Zocher 《Journal of molecular biology》2021,433(2):166726
Prenylation is a process widely prevalent in primary and secondary metabolism, contributing to functionality and chemical diversity in natural systems. Due to their high regio- and chemoselectivities, prenyltransferases are also valuable tools for creation of new compounds by chemoenzymatic synthesis and synthetic biology. Over the last ten years, biochemical and structural investigations shed light on the mechanism and key residues that control the catalytic process, but to date crucial information on how certain prenyltransferases control regioselectivity and chemoselectivity is still lacking. Here, we advance a general understanding of the enzyme family by contributing the first structure of a tryptophan C5-prenyltransferase 5-DMATS. Additinally, the structure of a bacterial tryptophan C6-prenyltransferase 6-DMATS was solved. Analysis and comparison of both substrate-bound complexes led to the identification of key residues for catalysis. Next, site-directed mutagenesis was successfully implemented to not only modify the prenyl donor specificity but also to redirect the prenylation, thereby switching the regioselectivity of 6-DMATS to that of 5-DMATS. The general strategy of structure-guided protein engineering should be applicable to other related prenyltransferases, thus enabling the production of novel prenylated compounds. 相似文献
87.
Unlike normal differentiated cells, tumor cells metabolize glucose via glycolysis under aerobic conditions, a hallmark of cancer known as the Warburg effect. Cells lacking the commonly mutated tumor suppressor PTEN exhibit a glycolytic phenotype reminiscent of the Warburg effect. This has been traditionally attributed to the hyperactivation of PI3K/Akt signaling that results from PTEN loss. Here, we propose a novel mechanism whereby the loss of PTEN negatively affects the activity of the E3 ligase APC/C-Cdh1, resulting in the stabilization of the enzyme PFKFB3 and increased synthesis of its product fructose 2,6-bisphosphate (F2,6P2). We discovered that when compared with wild-type cells, PTEN knock-out mouse embryonic fibroblasts (PTEN KO MEF) have 2–3-fold higher concentrations of F2,6P2, the most potent allosteric activator of the glycolytic enzyme phosphofructokinase-1 (PFK-1). Reintroduction of either wild-type or phosphatase mutant PTEN in the PTEN KO cells effectively lowers F2,6P2 to the wild-type levels and reduces their lactate production. PTEN KO cells were found to have high protein levels of PFKFB3, which directly contribute to the increased concentrations of F2,6P2. PTEN enhances interaction between PFKFB3 and Cdh1, and overexpression of Cdh1 down-regulates the PFKFB3 protein level in wild-type, but not in PTEN-deficient cells. Importantly, we found that the degradation of endogenous PFKFB3 in PTEN KO cells occurs at a slower rate than in wild-type cells. Our results suggest an important role for F2,6P2 in the metabolic reprogramming of PTEN-deficient cells that has important consequences for cell proliferation. 相似文献
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