Local migration promotes competitive restraint in a host-pathogen 'tragedy of the commons'

Fragmented populations possess an intriguing duplicity: even if subpopulations are reliably extinction-prone, asynchrony in local extinctions and recolonizations makes global persistence possible. Migration is a double-edged sword in such cases: too little migration prevents recolonization of extinct patches, whereas too much synchronizes subpopulations, raising the likelihood of global extinction. Both edges of this proverbial sword have been explored by manipulating the rate of migration within experimental populations. However, few experiments have examined how the evolutionary ecology of fragmented populations depends on the pattern of migration. Here, we show that the migration pattern affects both coexistence and evolution within a community of bacterial hosts (Escherichia coli) and viral pathogens (T4 coliphage) distributed across a large network of subpopulations. In particular, different patterns of migration select for distinct pathogen strategies, which we term 'rapacious' and 'prudent'. These strategies define a 'tragedy of the commons': rapacious phage displace prudent variants for shared host resources, but prudent phage are more productive when alone. We find that prudent phage dominate when migration is spatially restricted, while rapacious phage evolve under unrestricted migration. Thus, migration pattern alone can determine whether a de novo tragedy of the commons is resolved in favour of restraint.     

An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas

Metastasis is the process by which cancers spread to distinct sites in the body. It is the principal cause of death in individuals suffering from cancer. For some types of cancer, early detection of metastasis at lymph nodes close to the site of the primary tumor is pivotal for appropriate treatment. Because it can be difficult to detect lymph node metastases reliably, many individuals currently receive inappropriate treatment. We show here that DNA microarray gene-expression profiling can detect lymph node metastases for primary head and neck squamous cell carcinomas that arise in the oral cavity and oropharynx. The predictor, established with an 82-tumor training set, outperforms current clinical diagnosis when independently validated. The 102 predictor genes offer unique insights into the processes underlying metastasis. The results show that the metastatic state can be deciphered from the primary tumor gene-expression pattern and that treatment can be substantially improved.     

New gene functions in megakaryopoiesis and platelet formation

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.     

The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements

Piwi proteins and Piwi-interacting RNAs (piRNAs) have conserved functions in transposon silencing. The murine Piwi proteins Mili and Miwi2 (also called Piwil2 and Piwil4, respectively) direct epigenetic LINE1 and intracisternal A particle transposon silencing during genome reprogramming in the embryonic male germ line. Piwi proteins are proposed to be piRNA-guided endonucleases that initiate secondary piRNA biogenesis; however, the actual contribution of their endonuclease activities to piRNA biogenesis and transposon silencing remain unknown. To investigate the role of Piwi-catalysed endonucleolytic activity, we engineered point mutations in mice that substitute the second aspartic acid to an alanine in the DDH catalytic triad of Mili and Miwi2, generating the Mili(DAH) and Miwi2(DAH) alleles, respectively. Analysis of Mili-bound piRNAs from homozygous Mili(DAH) fetal gonadocytes revealed a failure of transposon piRNA amplification, resulting in the marked reduction of piRNA bound within Miwi2 ribonuclear particles. We find that Mili-mediated piRNA amplification is selectively required for LINE1, but not intracisternal A particle, silencing. The defective piRNA pathway in Mili(DAH) mice results in spermatogenic failure and sterility. Surprisingly, homozygous Miwi2(DAH) mice are fertile, transposon silencing is established normally and no defects in secondary piRNA biogenesis are observed. In addition, the hallmarks of piRNA amplification are observed in Miwi2-deficient gonadocytes. We conclude that cycles of intra-Mili secondary piRNA biogenesis fuel piRNA amplification that is absolutely required for LINE1 silencing.     

自我效能与员工动机性努力的关系研究

随着社会的不断进步,全球范围内的企业内部组织正在发生巨变,未来企业成功的关键是依靠企业人力资源,如何有效地组织、培训员工已经成为市场竞争中的核心内容之一,以人为本成为企业立足和发展的根本.管理者应有效地管理企业的人力资源,为企业提供强有力的储备力量,使之成为企业发展的主动力.而企业员工的自我效能是预测其绩效的最佳指标之一,因此对自我效能的深入研究将是未来的人力资源管理的趋势.     

Molecular mechanisms of kinetochore capture by spindle microtubules

For high-fidelity chromosome segregation, kinetochores must be properly captured by spindle microtubules, but the mechanisms underlying initial kinetochore capture have remained elusive. Here we visualized individual kinetochore-microtubule interactions in Saccharomyces cerevisiae by regulating the activity of a centromere. Kinetochores are captured by the side of microtubules extending from spindle poles, and are subsequently transported poleward along them. The microtubule extension from spindle poles requires microtubule plus-end-tracking proteins and the Ran GDP/GTP exchange factor. Distinct kinetochore components are used for kinetochore capture by microtubules and for ensuring subsequent sister kinetochore bi-orientation on the spindle. Kar3, a kinesin-14 family member, is one of the regulators that promote transport of captured kinetochores along microtubules. During such transport, kinetochores ensure that they do not slide off their associated microtubules by facilitating the conversion of microtubule dynamics from shrinkage to growth at the plus ends. This conversion is promoted by the transport of Stu2 from the captured kinetochores to the plus ends of microtubules.