Identification of stem cells in small intestine and colon by marker gene Lgr5

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. It is currently believed that four to six crypt stem cells reside at the +4 position immediately above the Paneth cells in the small intestine; colon stem cells remain undefined. Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49) was selected from a panel of intestinal Wnt target genes for its restricted crypt expression. Here, using two knock-in alleles, we reveal exclusive expression of Lgr5 in cycling columnar cells at the crypt base. In addition, Lgr5 was expressed in rare cells in several other tissues. Using an inducible Cre knock-in allele and the Rosa26-lacZ reporter strain, lineage-tracing experiments were performed in adult mice. The Lgr5-positive crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. The expression pattern of Lgr5 suggests that it marks stem cells in multiple adult tissues and cancers.     

Improved estimates of upper-ocean warming and multi-decadal sea-level rise

Changes in the climate system's energy budget are predominantly revealed in ocean temperatures and the associated thermal expansion contribution to sea-level rise. Climate models, however, do not reproduce the large decadal variability in globally averaged ocean heat content inferred from the sparse observational database, even when volcanic and other variable climate forcings are included. The sum of the observed contributions has also not adequately explained the overall multi-decadal rise. Here we report improved estimates of near-global ocean heat content and thermal expansion for the upper 300 m and 700 m of the ocean for 1950-2003, using statistical techniques that allow for sparse data coverage and applying recent corrections to reduce systematic biases in the most common ocean temperature observations. Our ocean warming and thermal expansion trends for 1961-2003 are about 50 per cent larger than earlier estimates but about 40 per cent smaller for 1993-2003, which is consistent with the recognition that previously estimated rates for the 1990s had a positive bias as a result of instrumental errors. On average, the decadal variability of the climate models with volcanic forcing now agrees approximately with the observations, but the modelled multi-decadal trends are smaller than observed. We add our observational estimate of upper-ocean thermal expansion to other contributions to sea-level rise and find that the sum of contributions from 1961 to 2003 is about 1.5 +/- 0.4 mm yr(-1), in good agreement with our updated estimate of near-global mean sea-level rise (using techniques established in earlier studies) of 1.6 +/- 0.2 mm yr(-1).     

Forecasting the economic recession in the U.K. 1979-1982: A comparison of model-based ex ante Forecasts

This paper compares the forecasts of recession and recovery made by five non-government U.K. teams modelling the economy (Cambridge Econometrics, the London Business School, the National Institute of Economic and Social Research, the Cambridge Economic Policy Group and the Liverpool Research Group). The paper concentrates on annual ex ante projections as published over the period 1978-1982, i.e. forecasts made, before the event, of the onset, length, depth and character of the economic recession in the U.K. which began in 1979. The comparison is in terms of year by year changes in production, unemployment, prices and other variables. It concludes that no group was systematically better or worse than other groups (confirming U.S. experience) and that the groups tended to perform better in their chosen areas of specialization, e.g. medium-term groups did better at forecasting the medium-term outcome.     

Developmental plasticity and human health

Many plants and animals are capable of developing in a variety of ways, forming characteristics that are well adapted to the environments in which they are likely to live. In adverse circumstances, for example, small size and slow metabolism can facilitate survival, whereas larger size and more rapid metabolism have advantages for reproductive success when resources are more abundant. Often these characteristics are induced in early life or are even set by cues to which their parents or grandparents were exposed. Individuals developmentally adapted to one environment may, however, be at risk when exposed to another when they are older. The biological evidence may be relevant to the understanding of human development and susceptibility to disease. As the nutritional state of many human mothers has improved around the world, the characteristics of their offspring--such as body size and metabolism--have also changed. Responsiveness to their mothers' condition before birth may generally prepare individuals so that they are best suited to the environment forecast by cues available in early life. Paradoxically, however, rapid improvements in nutrition and other environmental conditions may have damaging effects on the health of those people whose parents and grandparents lived in impoverished conditions. A fuller understanding of patterns of human plasticity in response to early nutrition and other environmental factors will have implications for the administration of public health.     

Geochemical tracing of Pacific-to-Atlantic upper-mantle flow through the Drake passage

The Earth's convecting upper mantle can be viewed as comprising three main reservoirs, beneath the Pacific, Atlantic and Indian oceans. Because of the uneven global distribution and migration of ridges and subduction zones, the surface area of the Pacific reservoir is at present contracting at about 0.6 km2 x y(r-1), while the Atlantic and Indian reservoirs are growing at about 0.45 km2 x yr(-1) and 0.15 km2 x yr(-1), respectively. Garfunkel and others have argued that there must accordingly be net mantle flow from the Pacific to the Atlantic and Indian reservoirs (in order to maintain mass balance), and Alvarez further predicted that this flow should be restricted to the few parts of the Pacific rim (here termed 'gateways') where there are no continental roots or subduction zones that might act as barriers to shallow mantle flow. The main Pacific gateways are, according to Alvarez, the southeast Indian Ocean, the Caribbean Sea and the Drake passage. Here we report geochemical data which confirm that there has been some outflow of Pacific mantle into the Drake passage--but probably in response to regional tectonic constraints, rather than global mass-balance requirements. We also show that a mantle domain boundary, equivalent to the Australian-Antarctic discordance, must lie between the Drake passage and the east Scotia Sea.