Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation

Enveloped viruses have evolved complex glycoprotein machinery that drives the fusion of viral and cellular membranes, permitting entry of the viral genome into the cell. For the paramyxoviruses, the fusion (F) protein catalyses this membrane merger and entry step, and it has been postulated that the F protein undergoes complex refolding during this process. Here we report the crystal structure of the parainfluenza virus 5 F protein in its prefusion conformation, stabilized by the addition of a carboxy-terminal trimerization domain. The structure of the F protein shows that there are profound conformational differences between the pre- and postfusion states, involving transformations in secondary and tertiary structure. The positions and structural transitions of key parts of the fusion machinery, including the hydrophobic fusion peptide and two helical heptad repeat regions, clarify the mechanism of membrane fusion mediated by the F protein.     

Frequency-dependent survival in natural guppy populations

The maintenance of genetic variation in traits under natural selection is a long-standing paradox in evolutionary biology. Of the processes capable of maintaining variation, negative frequency-dependent selection (where rare types are favoured by selection) is the most powerful, at least in theory; however, few experimental studies have confirmed that this process operates in nature. One of the most extreme, unexplained genetic polymorphisms is seen in the colour patterns of male guppies (Poecilia reticulata). Here we manipulated the frequencies of males with different colour patterns in three natural populations to estimate survival rates, and found that rare phenotypes had a highly significant survival advantage compared to common phenotypes. Evidence from humans and other species implicates frequency-dependent survival in the maintenance of molecular, morphological and health-related polymorphisms. As a controlled manipulation in nature, this study provides unequivocal support for frequency-dependent survival--an evolutionary process capable of maintaining extreme polymorphism.     

Independent evolution of bitter-taste sensitivity in humans and chimpanzees

It was reported over 65 years ago that chimpanzees, like humans, vary in taste sensitivity to the bitter compound phenylthiocarbamide (PTC). This was suggested to be the result of a shared balanced polymorphism, defining the first, and now classic, example of the effects of balancing selection in great apes. In humans, variable PTC sensitivity is largely controlled by the segregation of two common alleles at the TAS2R38 locus, which encode receptor variants with different ligand affinities. Here we show that PTC taste sensitivity in chimpanzees is also controlled by two common alleles of TAS2R38; however, neither of these alleles is shared with humans. Instead, a mutation of the initiation codon results in the use of an alternative downstream start codon and production of a truncated receptor variant that fails to respond to PTC in vitro. Association testing of PTC sensitivity in a cohort of captive chimpanzees confirmed that chimpanzee TAS2R38 genotype accurately predicts taster status in vivo. Therefore, although Fisher et al.'s observations were accurate, their explanation was wrong. Humans and chimpanzees share variable taste sensitivity to bitter compounds mediated by PTC receptor variants, but the molecular basis of this variation has arisen twice, independently, in the two species.     

A Brief Review of Peter B. Checkland's Contribution to Systemic Thinking

A brief review of Peter B. Checkland's contribution to systemic thinking is presented in five parts: (i) a thumbnail sketch of his life and works; (ii) to action research; (iii) to interpretive-based systemic theory; (iv) formulation of soft systems methodology; and (v) brief reflections.     

Insulin secretion and (pro)insulin biosynthesis of cultured mice islets after glibenclamide loading in vitro

Isolated islets from C57Bl/6J mice exposed to 10 mmoles/l glucose supplemented with 5 micrograms/ml glibenclamide for 48 h released significantly less insulin in the subsequent short-time incubation than untreated controls (without glibenclamide), whereas insulin biosynthesis was not suppressed by glibenclamide treatment.     

人类将掌握自身的进化

不论喜欢与否，在短短的几年里，人类将能掌握自身的进化。在会议厅里，遗传学家和发育生物学家坐在一起，讨论以往曾是不可想象的课题——转基因处理人类胚胎，使他们、他们的孩子、他们孩子的孩子，作出代代相传的改变。这些专家以惊人的坦率谈论用种系基因工程（genn－lineengineering）去治愈致命的疾病，甚至去产生更强壮、更俊美、更抗感染的设计好的婴儿。医生们正准备好作基因治疗试验，用相对少量改变好的细胞（例如肺里的）去纠正一个疾病；而种系基因工程可要改变全身的每个细胞。人们不再需以双亲的实际上不够满意的基因的偶然…