Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin

Nephronophthisis (NPHP) is the most frequent genetic cause of chronic renal failure in children. Identification of four genes mutated in NPHP subtypes 1-4 (refs. 4-9) has linked the pathogenesis of NPHP to ciliary functions. Ten percent of affected individuals have retinitis pigmentosa, constituting the renal-retinal Senior-Loken syndrome (SLSN). Here we identify, by positional cloning, mutations in an evolutionarily conserved gene, IQCB1 (also called NPHP5), as the most frequent cause of SLSN. IQCB1 encodes an IQ-domain protein, nephrocystin-5. All individuals with IQCB1 mutations have retinitis pigmentosa. Hence, we examined the interaction of nephrocystin-5 with RPGR (retinitis pigmentosa GTPase regulator), which is expressed in photoreceptor cilia and associated with 10-20% of retinitis pigmentosa. We show that nephrocystin-5, RPGR and calmodulin can be coimmunoprecipitated from retinal extracts, and that these proteins localize to connecting cilia of photoreceptors and to primary cilia of renal epithelial cells. Our studies emphasize the central role of ciliary dysfunction in the pathogenesis of SLSN.     

P-N~ -N-P锗漂移型三极管低频h参数的温度关系

样品的描述本工作测试了P-N~ -N-P锗漂移型三极管低频h参数的温度关系.所采用的样品是在高阻的N型锗基片上扩散一层强N型层,然后用合金方法在锗片两面制成P型区的发射极和集电极,其结构示意图如图1所示.     

MOSFET二维数值分析程序——TDAM

集成电路的发展要求不断缩小MOSFET的尺寸.用解析方法描述小尺寸器件有较大的局限性.为精确描述小尺寸器件,人们不得不求助于较复杂的数值方法. 本文提出一种适用于小型计算机的短沟MOSFET二维数值分析程序——TDAM.在处理基本方程时,对流函数作了简化,使运算收敛速度加快.在描述杂质分布时,结合解析和数值方法实现了二维模拟.TDAM同SUPREM-2联用,能从器件的工艺和几何参数出发预测物理特性和电特性.TDAM除能给出MOSFET的端子直流特性,还可提供二维载流子分布、电势分布、电流密度分布等用测量手段得不到的信息. 以下依次叙述物理模型、数学处理、程序概述、计算结果及讨论和结束语等.     

锗合金结及合金扩散结晶体管低频h参数的温度关系

一、引言晶体三极管电学参数随温度变化而发生的剧烈变化是限制它们在无线电设备中更广泛应用的重要原因之一.因此,研究晶体三极管电学参数的温度关系能为晶体管的更广泛应用提供有价值的参考资料;同时,把实验结果与理论计算相比较,还可检验理论的正确性.锗合金结P-N-P晶体三极管小讯号参数的温度关系已有一部分实验及理论工作,锗合金扩散结P-N-P晶体三极管小讯号参数温度关系的资料目前还较零星.本     

CMOS集成电路中闩锁效应的模拟

为了预测体硅OMOS电路中闩锁效应发生的条件,本文开发了一个改进的集总参数模型,以计算闩锁的维持特性与静态触发特性;提出了一个新的扩展电阻公式以代替费时的二维数值计算。模拟结果与实验数据吻合,对6微米工艺和等比例缩小的3微米工艺CMOS电路中的闩锁效应进行了计算和比较。     

TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum

Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ～5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders.     

水平排列硅光二极管色传感器及其特性

简要介绍水平排列硅光二极管色传感器的制作工艺，该器件波长在５００ｎｍ到６５０ｎｍ范围内有一个单调的近于线性的光谱响应。入射光波长为６００ｎｍ时，入射光强度化五个数量级，测出的波长基本不变，器件波长分辨率、最低入射光强、长时间测量的波长漂移以及波长温漂系数等特性的测量结果表明：该类色传感器已达高性能实用要求。     

Investigation of Sparse Data Mouse Imaging Using Micro-CT with a Carbon-Nanotube-Based X-ray Source

There has been a renewed interest in algorithm development for image reconstruction from highly incomplete data in computed tomography(CT).Such algorithms may lead to reduced imaging dose and time,and to the design of innovative configurations tailored to specific imaging tasks.In recent years,a carbon-nanotube(CNT)-based field-emission x-ray source has been developed,which offers easy electronic control of radiation and thus can be an ideal candidate for gated imaging.We have recently proposed algorithms f...     

Sexual selection enables long-term coexistence despite ecological equivalence

Empirical data indicate that sexual preferences are critical for maintaining species boundaries, yet theoretical work has suggested that, on their own, they can have only a minimal role in maintaining biodiversity. This is because long-term coexistence within overlapping ranges is thought to be unlikely in the absence of ecological differentiation. Here we challenge this widely held view by generalizing a standard model of sexual selection to include two ubiquitous features of populations with sexual selection: spatial variation in local carrying capacity, and mate-search costs in females. We show that, when these two features are combined, sexual preferences can single-handedly maintain coexistence, even when spatial variation in local carrying capacity is so slight that it might go unnoticed empirically. This theoretical study demonstrates that sexual selection alone can promote the long-term coexistence of ecologically equivalent species with overlapping ranges, and it thus provides a novel explanation for the maintenance of species diversity.     

Disruption of CREB function in brain leads to neurodegeneration

Control of cellular survival and proliferation is dependent on extracellular signals and is a prerequisite for ordered tissue development and maintenance. Activation of the cAMP responsive element binding protein (CREB) by phosphorylation has been implicated in the survival of mammalian cells. To define its roles in the mouse central nervous system, we disrupted Creb1 in brain of developing and adult mice using the Cre/loxP system. Mice with a Crem(-/-) background and lacking Creb in the central nervous system during development show extensive apoptosis of postmitotic neurons. By contrast, mice in which both Creb1 and Crem are disrupted in the postnatal forebrain show progressive neurodegeneration in the hippocampus and in the dorsolateral striatum. The striatal phenotype is reminiscent of Huntington disease and is consistent with the postulated role of CREB-mediated signaling in polyglutamine-triggered diseases.