Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart

Understanding cellular response to environmental stress has broad implications for human disease. AMP-activated protein kinase (AMPK) orchestrates the regulation of energy-generating and -consuming pathways, and protects the heart against ischaemic injury and apoptosis. A role for circulating hormones such as adiponectin and leptin in the activation of AMPK has received recent attention. Whether local autocrine and paracrine factors within target organs such as the heart modulate AMPK is unknown. Here we show that macrophage migration inhibitory factor (MIF), an upstream regulator of inflammation, is released in the ischaemic heart, where it stimulates AMPK activation through CD74, promotes glucose uptake and protects the heart during ischaemia-reperfusion injury. Germline deletion of the Mif gene impairs ischaemic AMPK signalling in the mouse heart. Human fibroblasts with a low-activity MIF promoter polymorphism have diminished MIF release and AMPK activation during hypoxia. Thus, MIF modulates the activation of the cardioprotective AMPK pathway during ischaemia, functionally linking inflammation and metabolism in the heart. We anticipate that genetic variation in MIF expression may impact on the response of the human heart to ischaemia by the AMPK pathway, and that diagnostic MIF genotyping might predict risk in patients with coronary artery disease.     

我国淡水水产品加工业的现状与前景展望

通过分析我国水产品养殖业和加工业的现状、存在问题以及人们将来对淡水水产品深精加工食品的需求趋势,指出我国应该大力发展淡水鱼的深精加工技术,生产淡水鱼深精加工方便食品,以满足人们对营养、方便、卫生食品的需求。     

Millennial- and orbital-scale changes in the East Asian monsoon over the past 224,000 years

High-resolution speleothem records from China have provided insights into the factors that control the strength of the East Asian monsoon. Our understanding of these factors remains incomplete, however, owing to gaps in the record of monsoon history over the past two interglacial-glacial cycles. In particular, missing sections have hampered our ability to test ideas about orbital-scale controls on the monsoon, the causes of millennial-scale events and relationships between changes in the monsoon and climate in other regions. Here we present an absolute-dated oxygen isotope record from Sanbao cave, central China, that completes a Chinese-cave-based record of the strength of the East Asian monsoon that covers the past 224,000 years. The record is dominated by 23,000-year-long cycles that are synchronous within dating errors with summer insolation at 65 degrees N (ref. 10), supporting the idea that tropical/subtropical monsoons respond dominantly and directly to changes in Northern Hemisphere summer insolation on orbital timescales. The cycles are punctuated by millennial-scale strong-summer-monsoon events (Chinese interstadials), and the new record allows us to identify the complete series of these events over the past two interglacial-glacial cycles. Their duration decreases and their frequency increases during glacial build-up in both the last and penultimate glacial periods, indicating that ice sheet size affects their character and pacing. The ages of the events are exceptionally well constrained and may thus serve as benchmarks for correlating and calibrating climate records.     

Lateral gene transfer and the nature of bacterial innovation

Unlike eukaryotes, which evolve principally through the modification of existing genetic information, bacteria have obtained a significant proportion of their genetic diversity through the acquisition of sequences from distantly related organisms. Horizontal gene transfer produces extremely dynamic genomes in which substantial amounts of DNA are introduced into and deleted from the chromosome. These lateral transfers have effectively changed the ecological and pathogenic character of bacterial species.     

Algae acquire vitamin B12 through a symbiotic relationship with bacteria

Vitamin B12 (cobalamin) was identified nearly 80 years ago as the anti-pernicious anaemia factor in liver, and its importance in human health and disease has resulted in much work on its uptake, cellular transport and utilization. Plants do not contain cobalamin because they have no cobalamin-dependent enzymes. Deficiencies are therefore common in strict vegetarians, and in the elderly, who are susceptible to an autoimmune disorder that prevents its efficient uptake. In contrast, many algae are rich in vitamin B12, with some species, such as Porphyra yezoensis (Nori), containing as much cobalamin as liver. Despite this, the role of the cofactor in algal metabolism remains unknown, as does the source of the vitamin for these organisms. A survey of 326 algal species revealed that 171 species require exogenous vitamin B12 for growth, implying that more than half of the algal kingdom are cobalamin auxotrophs. Here we show that the role of vitamin B12 in algal metabolism is primarily as a cofactor for vitamin B12-dependent methionine synthase, and that cobalamin auxotrophy has arisen numerous times throughout evolution, probably owing to the loss of the vitamin B12-independent form of the enzyme. The source of cobalamin seems to be bacteria, indicating an important and unsuspected symbiosis.     

Comparing partitions

The problem of comparing two different partitions of a finite set of objects reappears continually in the clustering literature. We begin by reviewing a well-known measure of partition correspondence often attributed to Rand (1971), discuss the issue of correcting this index for chance, and note that a recent normalization strategy developed by Morey and Agresti (1984) and adopted by others (e.g., Miligan and Cooper 1985) is based on an incorrect assumption. Then, the general problem of comparing partitions is approached indirectly by assessing the congruence of two proximity matrices using a simple cross-product measure. They are generated from corresponding partitions using various scoring rules. Special cases derivable include traditionally familiar statistics and/or ones tailored to weight certain object pairs differentially. Finally, we propose a measure based on the comparison of object triples having the advantage of a probabilistic interpretation in addition to being corrected for chance (i.e., assuming a constant value under a reasonable null hypothesis) and bounded between ±1.William H.E. Day was Acting Editor for the reviewing of this paper. We are grateful to him, Ove Frank, Charles Lewis, Glenn W. Milligan, Ivo Molenaar, Stanley S. Wasserman, and anonymous referees for helpful suggestions. Lynn Bilger and Tom Sharpe provided competent technical assistance. Partial support of Phipps Arabie's participation in this research was provided by NSF Grant SES 8310866 and ONR Contract N00014-83-K-0733.