Nesprin interchain associations control nuclear size

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.     

Mutations that silence constitutive signaling activity in the allosteric ligand-binding site of the thyrotropin receptor

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.     

高斯杂波中距离扩展目标的模糊CFAR检测

为提高高分辨雷达的检测性能,提出了一种高斯杂波背景下距离扩展目标的模糊检测方法。该方法采用模糊恒虚警率(constant false alarm rate, CFAR)检测器代替传统的二进制CFAR检测器,将距离单元值转换成映射到虚警空间的模糊隶属函数值,然后采用模糊积累准则进行积累,得到检测统计量。研究了模糊代数积、模糊代数和两种积累准则,推导出这两种方法虚警概率的数学解析式。仿真结果表明,高斯杂波背景下模糊代数积积累较双门限二进制积累可获得近2 dB的性能改善。同时,模糊检测方法只采用单个检测门限,具有易于调节的优点。     

Diethylmesoxalate hydrate, a new irreversible inhibitor of cholinesterases.

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.     

Regulation of grasshopper fecundity,longevity and egg viability by plant growth hormones

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.