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131.
132.
Rowbottom MW Vickers TD Tamiya J Zhang M Dyck B Grey J Schwarz D Heise CE Hedrick M Wen J Tang H Wang H Fisher A Aparicio A Saunders J Goodfellow VS 《Bioorganic & medicinal chemistry letters》2007,17(8):2171-2178
The design, synthesis, and SAR of a series of substituted spirohydantoins are described. Optimization of an in-house screening hit gave compounds that exhibited potent binding affinity and functional activity at MCH-R1. 相似文献
133.
Relief of hypoxia by angiogenesis promotes neural stem cell differentiation by targeting glycolysis 下载免费PDF全文
Christian Lange Miguel Turrero Garcia Ilaria Decimo Francesco Bifari Guy Eelen Annelies Quaegebeur Ruben Boon Hui Zhao Bram Boeckx Junlei Chang Christine Wu Ferdinand Le Noble Diether Lambrechts Mieke Dewerchin Calvin J Kuo Wieland B Huttner Peter Carmeliet 《The EMBO journal》2016,35(9):924-941
Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo‐spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel‐specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, suggesting that niche blood vessels regulate NSC differentiation at least in part by providing oxygen. Consistent herewith, hypoxia‐inducible factor (HIF)‐1α levels controlled the switch of NSC expansion to differentiation. Finally, we provide evidence that high glycolytic activity of NSCs is required to prevent their precocious differentiation in vivo. Thus, blood vessel function is required for efficient NSC differentiation in the developing cerebral cortex by providing oxygen and possibly regulating NSC metabolism. 相似文献
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Farrow PJ Barrett LB Stevenson M Fisher KD Finn J Spice R Allan MA Berry M Logan A Seymour LW Read ML 《Nucleic acids research》2006,34(11):e80
Non-viral vectors are promising vehicles for gene therapy but delivery of plasmid DNA to post-mitotic cells is challenging as nuclear entry is particularly inefficient. We have developed and evaluated a hybrid mRNA/DNA system designed to bypass the nuclear barrier to transfection and facilitate cytoplasmic gene expression. This system, based on co-delivery of mRNA(A64) encoding for T7 RNA polymerase (T7 RNAP) with a T7-driven plasmid, produced between 10- and 2200-fold higher gene expression in primary dorsal root ganglion neuronal (DRGN) cultures isolated from Sprague–Dawley rats compared to a cytomegalovirus (CMV)-driven plasmid, and 30-fold greater expression than the enhanced T7-based autogene plasmid pR011. Cell-free assays and in vitro transfections highlighted the versatility of this system with small quantities of T7 RNAP mRNA required to mediate expression at levels that were significantly greater than with the T7-driven plasmid alone or supplemented with T7 RNAP protein. We have also characterized a number of parameters, such as mRNA structure, intracellular stability and persistence of each nucleic acid component that represent important factors in determining the transfection efficiency of this hybrid expression system. The results from this study demonstrate that co-delivery of mRNA is a promising strategy to yield increased expression with plasmid DNA, and represents an important step towards improving the capability of non-viral vectors to mediate efficient gene transfer in cell types, such as in DRGN, where the nuclear membrane is a significant barrier to transfection. 相似文献
136.
Santiago LS Goldstein G Meinzer FC Fisher JB Machado K Woodruff D Jones T 《Oecologia》2004,140(4):543-550
We investigated how water transport capacity, wood density and wood anatomy were related to leaf photosynthetic traits in two lowland forests in Panama. Leaf-specific hydraulic conductivity (kL) of upper branches was positively correlated with maximum rates of net CO2 assimilation per unit leaf area (Aarea) and stomatal conductance (gs) across 20 species of canopy trees. Maximum kL showed stronger correlation with Aarea than initial kL suggesting that allocation to photosynthetic potential is proportional to maximum water transport capacity. Terminal branch kL was negatively correlated with Aarea/gs and positively correlated with photosynthesis per unit N, indicating a trade-off of efficient use of water against efficient use of N in photosynthesis as water transport efficiency varied. Specific hydraulic conductivity calculated from xylem anatomical characteristics (ktheoretical) was positively related to Aarea and kL, consistent with relationships among physiological measurements. Branch wood density was negatively correlated with wood water storage at saturation, kL, Aarea, net CO2 assimilation per unit leaf mass (Amass), and minimum leaf water potential measured on covered leaves, suggesting that wood density constrains physiological function to specific operating ranges. Kinetic and static indices of branch water transport capacity thus exhibit considerable co-ordination with allocation to potential carbon gain. Our results indicate that understanding tree hydraulic architecture provides added insights to comparisons of leaf level measurements among species, and links photosynthetic allocation patterns with branch hydraulic processes. 相似文献
137.
Stuart J. Collard Andrew M. Fisher David J. McKenna 《Ecological Management & Restoration》2011,12(1):37-45
Summary In the fragmented agricultural landscapes of temperate southern Australia, broad‐scale revegetation is underway to address multiple natural resource management issues. In particular, commercially‐driven fodder shrub plantings are increasingly being established on non‐saline land to fill the summer‐autumn feed gap in grazing systems. Little is known of the contribution that these and other planted woody perennial systems make to biodiversity conservation in multifunctional landscapes. In order to address this knowledge gap, a study was conducted in the southern Murray Mallee region of South Australia. Selected ecological indicators, including plant and bird communities, were sampled in spring 2008 and autumn 2009 in five planted saltbush sites and nearby areas of remnant vegetation and improved pasture. In general, remnant vegetation sites had higher biodiversity values than saltbush and pasture sites. Saltbush sites contained a diverse range of plants and birds, including a number of threatened bird species not found in adjacent pasture sites. Plant and bird communities showed significant variation across saltbush, pasture and remnant treatments and significant differences between seasons. This study demonstrates that saltbush plantings can provide at least partial habitat for some native biota within a highly modified agricultural landscape. Further research is being conducted on the way in which biota, such as birds, use available resources in these dynamic ecosystems. An examination of the effects of grazing on biodiversity in saltbush would improve the ability of landholders and regional natural resource management agencies in making informed land management decisions. 相似文献
138.
Daryl R. Chastain John L. Snider Guy D. Collins Calvin D. Perry Jared Whitaker Seth A. Byrd 《Journal of plant physiology》2014
Much effort has been expended to improve irrigation efficiency and drought tolerance of agronomic crops; however, a clear understanding of the physiological mechanisms that interact to decrease source strength and drive yield loss has not been attained. To elucidate the underlying mechanisms contributing to inhibition of net carbon assimilation under drought stress, three cultivars of Gossypium hirsutum were grown in the field under contrasting irrigation regimes during the 2012 and 2013 growing season near Camilla, Georgia, USA. Physiological measurements were conducted on three sample dates during each growing season (providing a broad range of plant water status) and included, predawn and midday leaf water potential (ΨPD and ΨMD), gross and net photosynthesis, dark respiration, photorespiration, and chlorophyll a fluorescence. End-of-season lint yield was also determined. ΨPD ranged from −0.31 to −0.95 MPa, and ΨMD ranged from −1.02 to −2.67 MPa, depending upon irrigation regime and sample date. G. hirsutum responded to water deficit by decreasing stomatal conductance, increasing photorespiration, and increasing the ratio of dark respiration to gross photosynthesis, thereby limiting PN and decreasing lint yield (lint yield declines observed during the 2012 growing season only). Conversely, even extreme water deficit, causing a 54% decline in PN, did not negatively affect actual quantum yield, maximum quantum yield, or photosynthetic electron transport. It is concluded that PN is primarily limited in drought-stressed G. hirsutum by decreased stomatal conductance, along with increases in respiratory and photorespiratory carbon losses, not inhibition or down-regulation of electron transport through photosystem II. It is further concluded that ΨPD is a reliable indicator of drought stress and the need for irrigation in field-grown cotton. 相似文献
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The mu agonist morphine and the non-specific opioid antagonist naloxone both may accelerate feline colonic transit; the effects of morphine are dose dependent. Kappa and delta receptor function was studied in the present work. Colonic transit of a radionuclide marker instilled into the cecum was quantitated for 6 hr in a crossover study. The delta agonist [D-Pen2,D-pen5]enkephalin (1 mg/kg, i.m.) prolonged the cecum and ascending colon half-emptying time by 337% (P less than 0.05), and delayed the progression of the geometric center over time. The kappa agonist U-50,488 (1 mg/kg, i.m.) had no apparent effect on the cecum and ascending colon, but delayed filling of the descending colon. Loperamide, an antidiarrheal agent, also delayed colonic transit. Thus, selective opioid agonists have both site and functional differences in their effect on feline colonic transit. 相似文献