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1.
Nesprins-1/-2/-3/-4 are nuclear envelope proteins, which connect nuclei to the cytoskeleton. The largest nesprin-1/-2 isoforms (termed giant) tether F-actin through their N-terminal actin binding domain (ABD). Nesprin-3, however, lacks an ABD and associates instead to plectin, which binds intermediate filaments. Nesprins are integrated into the outer nuclear membrane via their C-terminal KASH-domain. Here, we show that nesprin-1/-2 ABDs physically and functionally interact with nesprin-3. Thus, both ends of nesprin-1/-2 giant are integrated at the nuclear surface: via the C-terminal KASH-domain and the N-terminal ABD-nesprin-3 association. Interestingly, nesprin-2 ABD or KASH-domain overexpression leads to increased nuclear areas. Conversely, nesprin-2 mini (contains the ABD and KASH-domain but lacks the massive nesprin-2 giant rod segment) expression yields smaller nuclei. Nuclear shrinkage is further enhanced upon nesprin-3 co-expression or microfilament depolymerization. Our findings suggest that multivariate intermolecular nesprin interactions with the cytoskeleton form a lattice-like filamentous network covering the outer nuclear membrane, which determines nuclear size.  相似文献   
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The thyrotropin receptor (TSHR) exhibits elevated cAMP signaling in the basal state and becomes fully activated by thyrotropin. Previously we presented evidence that small-molecule ligands act allosterically within the transmembrane region in contrast to the orthosteric extracellular hormone-binding sites. Our goal in this study was to identify positions that surround the allosteric pocket and that are sensitive for inactivation of TSHR. Homology modeling combined with site-directed mutagenesis and functional characterization revealed seven mutants located in the allosteric binding site that led to a decrease of basal cAMP signaling activity. The majority of these silencing mutations, which constrain the TSHR in an inactive conformation, are found in two clusters when mapped onto the 3D structural model. We suggest that the amino acid positions identified herein are indicating locations where small-molecule antagonists, both neutral antagonists and inverse agonists, might interfere with active TSHR conformations.  相似文献   
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Summary Abscisic acid, a plant growth hormone, added in water to the grass diet of a grasshopper, greatly reduces the reproductive rate, as does gibberellin A3 at doses 10 times greater. Reciprocal seasonal variations in quantities of these hormones could synchronize the growth and reproduction of insects with their host plants in the field.Acknowledgments. I thank Drs J. Pickett, G. Strobel, D. Meyers, I. Mills, L. Jackson and J. Bradbury for helpful consultations; Dr R. Lund and Ms W. Whitmore for statistical analyses, and S. Baril, M. Gaudet, D. Wrobetz, J. Cotter and W. Wallace for technical assistance. This research was supported by the Montana Agricultural Experiment Station, Project 420, and is published as Journal Paper No. 865.  相似文献   
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G Voss  R Neumann 《Experientia》1979,35(5):583-584
Bovine erythrocyte acetylcholinesterase and human plasma cholinesterase are irreversibly inhibited by diethylmesoxalate hydrate, the inhibition potency being comparable to that of certian insecticidal organophosphates and carbamates. Insect cholinesterases, however, appear to be much less affected by diethylmesoxalate hydrate. The compound was also found to inhibit the hydrolysis of paraoxon by rabbit plasma A-esterase, but in a reversible mode.  相似文献   
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Shackleton crater is nearly coincident with the Moon's south pole. Its interior receives almost no direct sunlight and is a perennial cold trap, making Shackleton a promising candidate location in which to seek sequestered volatiles. However, previous orbital and Earth-based radar mapping and orbital optical imaging have yielded conflicting interpretations about the existence of volatiles. Here we present observations from the Lunar Orbiter Laser Altimeter on board the Lunar Reconnaissance Orbiter, revealing Shackleton to be an ancient, unusually well-preserved simple crater whose interior walls are fresher than its floor and rim. Shackleton floor deposits are nearly the same age as the rim, suggesting that little floor deposition has occurred since the crater formed more than three billion years ago. At a wavelength of 1,064 nanometres, the floor of Shackleton is brighter than the surrounding terrain and the interiors of nearby craters, but not as bright as the interior walls. The combined observations are explicable primarily by downslope movement of regolith on the walls exposing fresher underlying material. The relatively brighter crater floor is most simply explained by decreased space weathering due to shadowing, but a one-micrometre-thick layer containing about 20 per cent surficial ice is an alternative possibility.  相似文献   
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We investigate the consensus problem for classifications of three types: partitions, dendrograms, and n-trees For partitions or dendrograms, lattice polynomials define natural consensus functions We extend these lattice methods to n-trees, introducing a general class of consensus functions that includes the intersection consensus functions in current use These lattice consensus methods have a number of desirable mathematical properties We prove that they all satisfy the Pareto Axiom For each of the three classification types, we determine which lattice consensus functions satisfy the Betweenness AxiomAuthor partially supported by a research grant from the Faculty Research Committee, Bowling State University  相似文献   
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