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71.
Joost M. Woltering Freek J. Vonk Nabila Bardine Ioana L. Tuduce Walter Knöchel Antony J. Durston 《Developmental biology》2009,332(1):82-89
It is generally assumed that the characteristic deregionalized body plan of species with a snake-like morphology evolved through a corresponding homogenization of Hox gene expression domains along the primary axis. Here, we examine the expression of Hox genes in snake embryos and show that a collinear pattern of Hox expression is retained within the paraxial mesoderm of the trunk. Genes expressed at the anterior and most posterior, regionalized, parts of the skeleton correspond to the expected anatomical boundaries. Unexpectedly however, also the dorsal (thoracic), homogenous rib-bearing region of trunk, is regionalized by unconventional gradual anterior limits of Hox expression that are not obviously reflected in the skeletal anatomy. In the lateral plate mesoderm we also detect regionalized Hox expression yet the forelimb marker Tbx5 is not restricted to a rudimentary forelimb domain but is expressed throughout the entire flank region. Analysis of several Hox genes in a caecilian amphibian, which convergently evolved a deregionalized body plan, reveals a similar global collinear pattern of Hox expression. The differential expression of posterior, vertebra-modifying or even rib-suppressing Hox genes within the dorsal region is inconsistent with the homogeneity in vertebral identity. Our results suggest that the evolution of a deregionalized, snake-like body involved not only alterations in Hox gene cis-regulation but also a different downstream interpretation of the Hox code. 相似文献
72.
Woltering TJ Wichmann J Goetschi E Knoflach F Ballard TM Huwyler J Gatti S 《Bioorganic & medicinal chemistry letters》2010,20(23):6969-6974
This study completes a series of papers devoted to the characterization of the non-competitive mGluR2/3 antagonist properties of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives with particular emphasis on derivatizations compatible with brain penetration and in vivo activity. Especially the compounds bearing a para-pyridine consistently showed in vivo activity in rat behavioral models after oral administration, for example, blockade of the mGluR2/3 agonist LY354740-induced hypoactivity and improvement of a working memory deficit induced either by LY354740 or scopolamine in the delayed match to position task (DMTP). Moreover, combination studies with a cholinesterase inhibitor show apparent synergistic effects on working memory impairment induced by scopolamine. 相似文献
73.
74.
Woltering TJ Wichmann J Goetschi E Adam G Kew JN Knoflach F Ballard TM Huwyler J Mutel V Gatti S 《Bioorganic & medicinal chemistry letters》2008,18(8):2725-2729
A series of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives was evaluated as non-competitive mGluR2/3 antagonists. Replacement of the (2-aryl)-ethynyl-moiety in 8-position with smaller less lipophilic substituents produced compounds inhibiting the binding of [3H]-LY354740 to rat mGluR2 with low nanomolar affinity and consistent functional effect at both mGluR2 and mGluR3. These compounds were able to reverse LY354740-mediated inhibition of field excitatory postsynaptic potentials in the rat dentate gyrus and in vivo activity could be demonstrated by reversal of the LY354740-induced hypoactivity in mice after oral administration. 相似文献
75.
Chemical-induced apoptotic cell death in tomato cells: involvement of caspase-like proteases 总被引:16,自引:0,他引:16
A new system to study programmed cell death in plants is described. Tomato (Lycopersicon esculentum Mill.) suspension cells were induced to undergo programmed cell death by treatment with known inducers of apoptosis in mammalian
cells. This chemical-induced cell death was accompanied by the characteristic features of apoptosis in animal cells, such
as typical changes in nuclear morphology, the fragmentation of the nucleus and DNA fragmentation. In search of processes involved
in plant apoptotic cell death, specific enzyme inhibitors were tested for cell-death-inhibiting activity. Our results showed
that proteolysis plays a crucial role in apoptosis in plants. Furthermore, caspase-specific peptide inhibitors were found
to be potent inhibitors of the chemical-induced cell death in tomato cells, indicating that, as in animal systems, caspase-like
proteases are involved in the apoptotic cell death pathway in plants.
Received: 5 August 1999 / Accepted: 14 March 2000 相似文献
76.
77.
Fuselier JA Sun L Woltering SN Murphy WA Vasilevich N Coy DH 《Bioorganic & medicinal chemistry letters》2003,13(5):799-803
Peptide hormones are often rapidly internalized after binding to and activation of their receptors which are sometimes over-expressed on tumor cells. Thus, peptide ligands are increasingly being utilized for specific tumor cell targeting and internalization of radioactive isotopes for tumor imaging and for specifically delivering and internalizing cytotoxic moieties. Here, we describe a new carbamate linker system containing a series of built-in nucleophile assisted releasing (BINAR) groups which enable the 'fine-tuning' of intracellular cleavage rates of free cytotoxic agents containing reactive OH groups. Release rates were found to fit well with the chemical model and several conjugates of camptothecin and one of combretastatin were shown to have potent cytotoxic effects on cultures of human neuroblastoma IMR-32 cells which over-express somatostatin receptors. 相似文献
78.
Weigand S Bischoff H Dittrich-Wengenroth E Heckroth H Lang D Vaupel A Woltering M 《Bioorganic & medicinal chemistry letters》2005,15(20):4619-4623
We report the solid-phase synthesis and pharmacological evaluation of a new series of small-molecule agonists of the human peroxisome proliferator-activated receptor delta (PPARdelta) based on a lead structure from our PPARalpha program. Compound 33 showed good pharmacokinetics. 相似文献
79.
Use of a laser-driven photoacoustic detection system for measurement of ethylene production in cymbidium flowers 总被引:3,自引:3,他引:0
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A laser-based photoacoustic method was used for determination of ethylene (C2H4) production of emasculated orchid (Cymbidium) flowers in a flow-through system. The laser photoacoustic equipment consisted of a line-tuneable CO2 laser in conjunction with a single-pass resonant acoustic cell. The minimum detection limit of the system for C2H4 in air was 0.03 nanoliter per liter. C2H4 production of intact Cymbidium (cv Mary Pinchess `Del Rey') flowers was very low (0.015 nanoliter per gram per hour) and showed an increase within 3 hours following emasculation (removal of pollinia plus anthercap). Production peaked (0.14 nanoliter per gram per hour) 8 hours after emasculation and decreased thereafter. Production again increased 45 hours after emasculation. Coloration of the labellum appeared shortly after the first peak; wilting of the petals and sepals appeared during the second rise in ethylene production. The use of the laser photoacoustic technique in plant physiological studies is discussed. 相似文献
80.