'Inverse' melting of a vortex lattice

Inverse melting is the process in which a crystal reversibly transforms into a liquid or amorphous phase when its temperature is decreased. Such a process is considered to be very rare, and the search for it is often hampered by the formation of non-equilibrium states or intermediate phases. Here we report the discovery of first-order inverse melting of the lattice formed by magnetic flux lines in a high-temperature superconductor. At low temperatures, disorder in the material pins the vortices, preventing the observation of their equilibrium properties and therefore the determination of whether a phase transition occurs. But by using a technique to 'dither' the vortices, we were able to equilibrate the lattice, which enabled us to obtain direct thermodynamic evidence of inverse melting of the ordered lattice into a disordered vortex phase as the temperature is decreased. The ordered lattice has larger entropy than the low-temperature disordered phase. The mechanism of the first-order phase transition changes gradually from thermally induced melting at high temperatures to a disorder-induced transition at low temperatures.     

Modifying with mitochondria

An elegant set of mouse crosses has been used to identify a mitochondrial variant that interacts with a nuclear locus on chromosome 10, Ahl, to modify age-related hearing loss. This discovery sets the stage for the identification of factors that modify expression levels and variability of human hearing impairments.     

基于NADH荧光的组织病理生理状态多参数在体监测与评价

组织病理生理状态的实时多参数评价, 无论在动物实验研究还是临床应用中均具有重要价值, 一直是生命科学与医学研究者们广泛关注的热点. 众所周知, 临床手术过程或重症监护病房中, 患者病理生理状态的实时监测是十分必需的. 心、脑等重要组织脏器是否处于缺血缺氧等危急状态直接关系到病人的存活与否; 早期发现术中和术后次要脏器的微循环障碍有助于提高器官移植等手术的成功率和降低术后并发症的发生率. 临床常规使用的监测指标, 如血压、心电、脉搏等, 在生命指征的实时评价中发挥了重要作用. 然而, 目前的常规指标尚不足以从分子水平反映局部组织病理生理状态的早期改变. NADH是细胞线粒体中氧化还原呼吸链上的内源性关键分子, 具有自发荧光性质, 可作为一项灵敏的内源性含氧状态指标来反映机体的代谢状态和细胞活力. 本文介绍了基于NADH自发荧光信号的细胞氧化还原状态在体监测方法, 从分子水平预警机体的活力情况, 结合微循环血流、血氧饱和度等多种生理参数的同步并行监测, 不仅可在活体动物体内进行疾病的病理生理学机制研究和新药的药效评价, 还有望应用于临床外科手术和重症监护病房, 为机体活力和生命指征的实时监护提供分子水平的动态信息. 目前, NADH荧光一维信号的获取技术发展最为成熟, 可实现从离体、活细胞、活体动物乃至临床水平的实时动态监测, 已处于临床推广应用阶段. 二维动态成像也已经发展到活体动物实验阶段. 三维成像由于受制于NADH荧光的穿透能力, 只能在冷冻组织切片上实现. 如何突破因高散射所致的荧光穿透能力受限的瓶颈, 最大限度地减少环境因素对荧光信号的干扰, 在分子水平实现组织病理生理状态的实时多参数评价, 是生物医学光子学领域面临的巨大挑战.     

Genome-wide, large-scale production of mutant mice by ENU mutagenesis

In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper, leads to a significant increase in the number of mouse models available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html).     

Beethoven, a mouse model for dominant, progressive hearing loss DFNA36

Despite recent progress in identifying genes underlying deafness, there are still relatively few mouse models of specific forms of human deafness. Here we describe the phenotype of the Beethoven (Bth) mouse mutant and a missense mutation in Tmc1 (transmembrane cochlear-expressed gene 1). Progressive hearing loss (DFNA36) and profound congenital deafness (DFNB7/B11) are caused by dominant and recessive mutations of the human ortholog, TMC1 (ref. 1), for which Bth and deafness (dn) are mouse models, respectively.