Physiogenomic resources for rat models of heart, lung and blood disorders

Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation.     

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.     

Comparative genome sequencing of Escherichia coli allows observation of bacterial evolution on a laboratory timescale

We applied whole-genome resequencing of Escherichia coli to monitor the acquisition and fixation of mutations that conveyed a selective growth advantage during adaptation to a glycerol-based growth medium. We identified 13 different de novo mutations in five different E. coli strains and monitored their fixation over a 44-d period of adaptation. We obtained proof that the observed spontaneous mutations were responsible for improved fitness by creating single, double and triple site-directed mutants that had growth rates matching those of the evolved strains. The success of this new genome-scale approach indicates that real-time evolution studies will now be practical in a wide variety of contexts.     

Tension directly stabilizes reconstituted kinetochore-microtubule attachments

Kinetochores are macromolecular machines that couple chromosomes to dynamic microtubule tips during cell division, thereby generating force to segregate the chromosomes. Accurate segregation depends on selective stabilization of correct 'bi-oriented' kinetochore-microtubule attachments, which come under tension as the result of opposing forces exerted by microtubules. Tension is thought to stabilize these bi-oriented attachments indirectly, by suppressing the destabilizing activity of a kinase, Aurora B. However, a complete mechanistic understanding of the role of tension requires reconstitution of kinetochore-microtubule attachments for biochemical and biophysical analyses in vitro. Here we show that native kinetochore particles retaining the majority of kinetochore proteins can be purified from budding yeast and used to reconstitute dynamic microtubule attachments. Individual kinetochore particles maintain load-bearing associations with assembling and disassembling ends of single microtubules for >30?min, providing a close match to the persistent coupling seen in vivo between budding yeast kinetochores and single microtubules. Moreover, tension increases the lifetimes of the reconstituted attachments directly, through a catch bond-like mechanism that does not require Aurora B. On the basis of these findings, we propose that tension selectively stabilizes proper kinetochore-microtubule attachments in vivo through a combination of direct mechanical stabilization and tension-dependent phosphoregulation.     

澳大利亚新英格兰地区桉树林的群落结构特征

本文研究澳大利亚新英格兰地区开阔林的群落结构特征。结果表明其种类组成较为简单,调查的4.8公顷样地中树木层只有18种。隶属于4属4科,树木个体90％为桉树;灌木层有32种19属13科;草本层有95种20属10科。群落的垂直结构为三层:树层,灌木层和草本层;一些林段只有二层(缺灌木层),或四层(增多小树层)。优势种群的分布格局多为集群分布。非优势种群的分布格局则多为随机分布格局。种间联结现象较弱,除少数种对外,联结系数低或没有联结。种间生态位的重叠值低,反映了诸多种群的独立分布特征。在其组织结构水平上,除草本层外。物种多样性指数、群落均匀度、生态优势度均较低。反映群落的优势种明显,为种多群落类型。     

Does environmental science crowd out non-epistemic values?

While no one denies that science depends on epistemic values, many philosophers of science have wrestled with the appropriate role of non-epistemic values, such as social, ethical, and political values. Recently, philosophers of science have overwhelmingly accepted that non-epistemic values should play a legitimate role in science. The recent philosophical debate has shifted from the value-free ideal in science to questions about how science should incorporate non-epistemic values. This article engages with such questions through an exploration of the environmental sciences. These sciences are a mosaic of diverse fields characterized by interdisciplinarity, problem-orientation, policy-directedness, and ubiquitous non-epistemic values. This article addresses a frequently voiced concern about many environmental science practices: that they ‘crowd out’ or displace significant non-epistemic values by either (1) entailing some non-epistemic values, rather than others, or by (2) obscuring discussion of non-epistemic values altogether. With three detailed case studies – monetizing nature, nature-society dualism, and ecosystem health – we show that the alleged problem of crowding out emerges from active debates within the environmental sciences. In each case, critics charge that the scientific practice in question displaces non-epistemic values in at least one of the two senses distinguished above. We show that crowding out is neither necessary nor always harmful when it occurs. However, we do see these putative objections to the application of environmental science as teaching valuable lessons about what matters for successful environmental science, all things considered. Given the significant role that many environmental scientists see for non-epistemic values in their fields, we argue that these cases motivate lessons about the importance of value-flexibility (that practices can accommodate a plurality of non-epistemic values), transparency about value-based decisions that inform practice, and environmental pragmatism.