《科学》杂志主编唐纳德·肯尼丹论述2001年度的重大科技进展

每一年 ,《Ｓｃｉｅｎｃｅ》杂志的编辑们都要聚在一起讨论该年度重大科技进展的提名问题。面对众多的新发现 ,往往是很具有挑战性的。今年我们遇到了一个尤为困难的任务 :找到一个能够和果蝇以及其他生命体的基因组测序相当的科技成就。果蝇以及其他生命体的基因组测序这项成果不仅仅席卷了去年的重大科技进展奖 ,而且它还导致了众多的后续项目 ,这决不亚于人类基因组草图的发表。这些后续的成功成了本年度科学中无人认领的珍宝中的一部分 ,而且就像去年一样完好的保存着。本年度重大科技进展的提名像去年的一样使人难忘 ,它涉及了从纳米技…     

Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene.

Proteolipid protein (PLP; M(r) 30,000) is a highly conserved major polytopic membrane protein in myelin but its cellular function remains obscure. Neurological mutant mice can often provide model systems for human genetic disorders. Mutations of the X-chromosome-linked PLP gene are lethal, identified first in the jimpy mouse and subsequently in patients with Pelizaeus-Merzbacher disease. The unexplained phenotype of these mutations includes degeneration and premature cell death of oligodendrocytes with associated hypomyelination. Here we show that a new mouse mutant rumpshaker is defined by the amino-acid substitution Ile-to-Thr at residue 186 in a membrane-embedded domain of PLP. Surprisingly, rumpshaker mice, although myelin-deficient, have normal longevity and a full complement of morphologically normal oligodendrocytes. Hypomyelination can thus be genetically separated from the PLP-dependent oligodendrocyte degeneration. We suggest that PLP has a vital function in glial cell development, distinct from its later role in myelin assembly, and that this dichotomy of action may explain the clinical spectrum of Pelizaeus-Merzbacher disease.     

Biodiversity as a barrier to ecological invasion

Biological invasions are a pervasive and costly environmental problem that has been the focus of intense management and research activities over the past half century. Yet accurate predictions of community susceptibility to invasion remain elusive. The diversity resistance hypothesis, which argues that diverse communities are highly competitive and readily resist invasion, is supported by both theory and experimental studies conducted at small spatial scales. However, there is also convincing evidence that the relationship between the diversity of native and invading species is positive when measured at regional scales. Although this latter relationship may arise from extrinsic factors, such as resource heterogeneity, that covary with diversity of native and invading species at large scales, the mechanisms conferring greater invasion resistance to diverse communities at local scales remain unknown. Using neighbourhood analyses, a technique from plant competition studies, we show here that species diversity in small experimental grassland plots enhances invasion resistance by increasing crowding and species richness in localized plant neighbourhoods. Both the establishment (number of invaders) and success (proportion of invaders that are large) of invading plants are reduced. These results suggest that local biodiversity represents an important line of defence against the spread of invaders.     

Introduction: lipid-binding proteins: novel aspects

Lipid-binding proteins function to transport lipids across membranes and aqueous phases and act to solubilise their cargo, protect it from chemical damage and probably also to define its destination. As such, they have been adapted to carry out a broad spectrum of biological functions in addition to their classical roles in energy metabolism and the transmission or blocking of retinoid-based signalling. The set of reviews in this issue of CMLS is designed to draw attention to some newly understood aspects and principles of their biology and structure, and concentrates on the proteins involved in transport of fatty acids and retinoids.     

Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population

The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1(+) (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages. To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDR(low)/C-KIT(CD117)(neg) population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDR(low)/C-KIT(neg) cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDR(low)/C-KIT(neg) fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.