诺贝尔医学生理奖:蛋白质地址编码之旅

在前几年里,诺贝尔医学奖的颁发曾引起过争议.例如,作为1997年度诺贝尔医学奖获奖成果的"关于‘普利昂’(prion)这种蛋白质能充当传染因子的理论",至今仍受到怀疑.但是,1999年度诺贝尔医学生理学奖的颁发却似乎是不容置疑的.     

Distribution and abundance of pelagic fish in Lake Powell, Utah, and Lake Mead, Arizona-Nevada

Pelagic fish communities (waters with depths > 20 m) of Lakes Powell and Mead were examined quarterly from 1995 to1998 using vertical gill nets and a scientific echosounder. Nets captured a total of 449 fish consisting of striped bass (57%/45% [Lake Powell/Lake Mead]), threadfin shad (24%/50%), common carp (15%/4%), walleye (3%), channel catfish (2%), and rainbow trout ( -1 ). Reservoirs experienced dramatic seasonal and annual fluctuations in pelagic biomass. Lake Powell's biomass peaked at the Colorado River at 709.7 (± 46.5) kg · ha -1 and Lake Mead's reached 291.9 (± 58.2) kg · ha -1 at Las Vegas Wash. These locations supported estimated fish densities of 124,668 fish · ha -1 and 15,131 fish · ha -1 , respectively. Maximum reservoir biomass peaked in August 1996, with Lake Powell supporting 10,852,738 ± 5,195,556 kg (27.6 × 10 7 fish) and Lake Mead 1,926,697 ± 892.994 kg (10.8 × 10 7 fish). Biomass ebbed in May (1996 and 1997), when Lake Mead supported 65% (296,736 kg vs. 453,097 kg) and 62% (101,016 kg vs. 162,262 kg) of biomass levels found in Lake Powell.     

Common nonsynonymous variants in PCSK1 confer risk of obesity

Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.     

Whole-lake carbon-13 additions reveal terrestrial support of aquatic food webs

Ecosystems are supported by organic carbon from two distinct sources. Endogenous carbon is produced by photosynthesis within an ecosystem by autotrophic organisms. Exogenous carbon is produced elsewhere and transported into ecosystems. Consumers may use exogenous carbon with consequent influences on population dynamics, predator-prey relationships and ecosystem processes. For example, exogenous inputs provide resources that may enhance consumer abundance beyond levels supported by within-system primary production. Exogenous fluxes of organic carbon to ecosystems are often large, but this material is recalcitrant and difficult to assimilate, in contrast to endogenously produced organic matter, which is used more easily. Here we show, by the experimental manipulation of dissolved inorganic (13)C in two lakes, that internal primary production is insufficient to support the food webs of these ecosystems. Additions of NaH(13)CO(3) enriched the (13)C content of dissolved inorganic carbon, particulate organic carbon, zooplankton and fish. Dynamics of (13)C indicate that 40-55% of particulate organic carbon and 22-50% of zooplankton carbon are derived from terrestrial sources, showing that there is significant subsidy of these ecosystems by organic carbon produced outside their boundaries.     

Proof-analysis and Continuity

During the first phase of Greek mathematics a proof consisted in showing or making visible the truth of a statement. This was the epagogic method. This first phase was followed by an apagogic or deductive phase. During this phase visual evidence was rejected and Greek mathematics became a deductive system. Now epagoge and apagoge, apart from being distinguished, roughly according to the modern distinction between inductive and deductive procedures, were also identified on account of the conception of generality as continuity. Epistemology of mathematics today only remembers the distinction, forgetting where they agreed, in this manner not only destroying the unity of the perceptual and conceptual but also forgetting what could be gained from Aristotelian demonstrative science.     

The theory theory thrice over: the child as scientist, Superscientist or social institution?

Alison Gopnik and Andrew Meltzoff have argued for a view they call the ‘theory theory’: theory change in science and children are similar. While their version of the theory theory has been criticized for depending on a number of disputed claims, we argue that there is a fundamental problem which is much more basic: the theory theory is multiply ambiguous. We show that it might be claiming that a similarity holds between theory change in children and (i) individual scientists, (ii) a rational reconstruction of a Superscientist, or (iii) the scientific community. We argue that (i) is false, (ii) is non-empirical (which is problematic since the theory theory is supposed to be a bold empirical hypothesis), and (iii) is either false or doesn't make enough sense to have a truth-value. We conclude that the theory theory is an interesting failure. Its failure points the way to a full, empirical picture of scientific development, one that marries a concern with the social dynamics of science to a psychological theory of scientific cognition.     

Prediction of central nervous system embryonal tumour outcome based on gene expression.

Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.