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951.
Background
Understanding how stability and/or maneuverability affects motor control strategies can provide insight on moving about safely in an unpredictable world. Stability in human movement has been well-studied while maneuverability has not. Further, a tradeoff between stability and maneuverability during movement seems apparent, yet has not been quantified. We proposed that greater maneuverability, the ability to rapidly and purposefully change movement direction and speed, is beneficial in uncertain environments. We also hypothesized that gaining maneuverability comes at the expense of stability and perhaps also corresponds with decreased muscle coactivation.Materials and Methods
We used a goal-directed forward lean movement task that integrated both stability and maneuverability. Subjects (n = 11) used their center of pressure to control a cursor on a computer monitor to reach a target. We added task uncertainty by shifting the target anterior-posterior position mid-movement. We used a balance board with a narrow beam that reduced the base of support in the medio-lateral direction and defined stability as the probability that subjects could keep the balance board level during the task.Results
During the uncertainty condition, subjects were able to change direction of their anterior-posterior center of pressure more rapidly, indicating that subjects were more maneuverable. Furthermore, medio-lateral center of pressure excursions also approached the edges of the beam and reduced stability margins, implying that subjects were less stable (i.e. less able to keep the board level). On the narrow beam board, subjects increased muscle coactivation of lateral muscle pairs and had greater muscle activity in the left leg. However, there were no statistically significant differences in muscle activity amplitudes or coactivation with uncertainty.Conclusions/Significance
These results demonstrate that there is a tradeoff between stability and maneuverability during a goal-directed whole-body movement. Tasks with added uncertainty could help individuals learn to be more maneuverable yet sufficiently stable. 相似文献952.
Thomas M Huang WS Wen D Zhu X Wang Y Metcalf CA Liu S Chen I Romero J Zou D Sundaramoorthi R Li F Qi J Cai L Zhou T Commodore L Xu Q Keats J Wang F Wardwell S Ning Y Snodgrass JT Broudy MI Russian K Iuliucci J Rivera VM Sawyer TK Dalgarno DC Clackson T Shakespeare WC 《Bioorganic & medicinal chemistry letters》2011,21(12):3743-3748
Ponatinib (AP24534) was previously identified as a pan-BCR-ABL inhibitor that potently inhibits the T315I gatekeeper mutant, and has advanced into clinical development for the treatment of refractory or resistant CML. In this study, we explored a novel series of five and six membered monocycles as alternate hinge-binding templates to replace the 6,5-fused imidazopyridazine core of ponatinib. Like ponatinib, these monocycles are tethered to pendant toluanilides via an ethynyl linker. Several compounds in this series displayed excellent in vitro potency against both native BCR-ABL and the T315I mutant. Notably, a subset of inhibitors exhibited desirable PK and were orally active in a mouse model of T315I-driven CML. 相似文献
953.
The bone morphogenetic protein-1 (BMP1)-like metalloproteinases play key roles in extracellular matrix formation, by converting precursors into mature functional proteins involved in forming the extracellular matrix. The BMP1-like proteinases also play roles in activating growth factors, such as BMP2/4, myostatin, growth differentiation factor 11, and transforming growth factor β1, by cleaving extracellular antagonists. The extracellular insulin-like growth factor-binding proteins (IGFBPs) are involved in regulating the effects of insulin-like growth factors (IGFs) on growth, development, and metabolism. Of the six IGFBPs, IGFBP3 has the greatest interaction with the large pool of circulating IGFs. It is also produced locally in tissues and is itself regulated by proteolytic processing. Here, we show that BMP1 cleaves human and mouse IGFBP3 at a single conserved site, resulting in markedly reduced ability of cleaved IGFBP3 to bind IGF-I or to block IGF-I-induced cell signaling. In contrast, such cleavage is shown to result in enhanced IGF-I-independent ability of cleaved IGFBP3 to block FGF-induced proliferation and to induce Smad phosphorylation. Consistent with in vivo roles for such cleavage, it is shown that, whereas wild type mouse embryo fibroblasts (MEFs) produce cleaved IGFBP3, MEFs doubly null for the Bmp1 gene and for the Tll1 gene, which encodes the related metalloproteinase mammalian Tolloid-like 1 (mTLL1), produce only unprocessed IGFBP3, thus demonstrating endogenous BMP1-related proteinases to be responsible for IGFBP3-processing activity in MEFs. Similarly, in zebrafish embryos, overexpression of Bmp1a is shown to reverse an Igfbp3-induced phenotype, consistent with the ability of BMP1-like proteinases to cleave IGFBP3 in vivo. 相似文献
954.
955.
Quox—1基因同源序列在人胚早期发育中的表达 总被引:3,自引:0,他引:3
以Quox-1基因的特异性片段b2为探针与人基因DNA作Southern杂交,结果显示,人基因组中存在Quox-1基因的同源序列。结果表明其表达有明显的时间和空间特异性。胚龄30天以前,Quox-1基因的同源序列在人胚包神经管等许多部位表达,30天以后表达部位局限于脊索、心肌细胞、生机节、消化道上皮及周皮等处。 相似文献
956.
957.
P. Schmitt C. Vasseur V. Phalip D. Q. Huang C. Diviès H. Prévost 《Applied microbiology and biotechnology》1997,47(6):715-718
The co-metabolism of citrate plus xylose by Leuconostoc mesenteroides subsp. mesenteroides results in a growth stimulation, an increase in d-lactate and acetate production and repression of ethanol production. This correlated well with the levels of key enzymes
involved. A partial repression of alcohol dehydrogenase and a marked stimulation of acetate kinase were observed. High citrate
bioconversion yields in diacetyl plus acetoin were obtained at pH 5.2 in batch (11.5%) or in chemostat (up to 17.4%) culture.
In contrast, no diacetyl or acetoin was detected in citrate plus glucose fermentation.
Received: 6 December 1996 / Received revision: 14 February 1997 / Accepted: 14 February 1997 相似文献
958.
On the specificity of human gastricsin and pepsin 总被引:2,自引:0,他引:2
959.
On the mechanism of activation of the ATP X Mg(II)-dependent phosphoprotein phosphatase by kinase FA 总被引:4,自引:0,他引:4
S Jurgensen E Shacter C Y Huang P B Chock S D Yang J R Vandenheede W Merlevede 《The Journal of biological chemistry》1984,259(9):5864-5870
The mechanism of activation of the Mg(II) X ATP-dependent phosphatase by the kinase FA has been investigated. The inactive protein phosphatase can be represented as FC X M where FC is the inactive catalytic component and M is the heat-stable modulator protein (also known as inhibitor-2). Phosphorylation of the modulator protein is demonstrated during activation of FC X M. In addition, continuous ATP hydrolysis during the activation is observed. This suggests that a cyclic phosphorylation-dephosphorylation reaction is continuously occurring during the activation. It is proposed that phosphorylation of the modulator protein causes an isomerization in FC to generate an active phosphatase. The activated phosphatase is capable of dephosphorylating the phosphorylated modulator. Upon dephosphorylation of modulator, the active phosphatase returns to its inactive form via a slow isomerization. 相似文献
960.