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。     

Distribution of Brechmorhoga clubskimmers (Odonata: Libellulidae) in the Grand Canyon region, southwestern USA

We examined the distribution of Brechmorhoga mendax and B. pertinax (Libellulidae) in northern Arizona and southern Nevada. Brechmorhoga mendax occurs widely throughout the Southwest and in Arizona up to the Mogollon Rim, and up the Colorado River from the west to at least River Mile 132 (downstream from Lees Ferry, Arizona) at elevations of 110-1460 m. In Grand Canyon it occurs along small to large tributaries and on the mainstream at elevations below 650 m. The only previously reported locality for B. pertinax in the United States is in southeastern Arizona, where it was presumed to be accidental. We report B. pertinax along 5 small, perennial tributaries emanating from Redwall Formation aquifer springs on the south side of central Grand Canyon. Those springs habitats may be threatened by regional groundwater depletion. Brechmorhoga pertinax appears to be somewhat more stenotolerant in its habitat requirements than B. mendax , a finding in keeping with these differences in range. The presence of isolated populations of B. pertinax in Grand Canyon is an example of a Neotropical influence on the fauna and indicates biogeographic corridor and refuge functions of this large, deep canyon.     

Facilitation of Yucca brevifolia recruitment by Mojave Desert shrubs

Patterns of recruitment for Yucca brevifolia (Joshua tree) were investigated on 3 elevational transects, 1000-2000 m, in the Spring and Sheep Mountain ranges of southern Nevada. Yucca brevifolia is distributed throughout a broad range of plant communities dominated by Larrea tridentata and Ambrosia dumosa at low elevations, Coleogyne ramosissima at middle elevations, and an Artemisia-Pinus-Juniperus community at upper elevations. The density of Y. brevifolia gradually increased from the lowest elevations, peaked at 1600 m, and remained at intermediate levels at high elevations until reaching an abrupt upper elevational limit at 2000 m. Open substrate dominated the study areas; however, a large majority of Y. brevifolia seedlings were found growing under the canopy of other woody shrubs. This pattern of recruitment did not vary by site or elevation. Thirty-five species of perennial shrubs were identified in the study areas, 16 of which were found in association with at least 1 Y. brevifolia seedling. However, 4 shrubs were found in a nurse plant relationship with Y. brevifolia above the frequency predicted by either their canopy area or numerical dominance. Seedlings exhibited significant variation in aspect, relative to the center of the nurse shrub. In Lee and Lucky Strike canyons, recruitment occurred predominantly on the east and west sides of nurse shrubs, indicating the importance of specific microhabitats. Local presence of specific perennial shrubs resulted in higher levels of recruitment, causing a distinct pattern of community development, resumably through amelioration of abiotic stresses.     

A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia

Phosphodiesterases (PDEs) regulate cyclic nucleotide levels. Increased cyclic AMP (cAMP) signaling has been associated with PRKAR1A or GNAS mutations and leads to adrenocortical tumors and Cushing syndrome. We investigated the genetic source of Cushing syndrome in individuals with adrenocortical hyperplasia that was not caused by known defects. We performed genome-wide SNP genotyping, including the adrenocortical tumor DNA. The region with the highest probability to harbor a susceptibility gene by loss of heterozygosity (LOH) and other analyses was 2q31-2q35. We identified mutations disrupting the expression of the PDE11A isoform-4 gene (PDE11A) in three kindreds. Tumor tissues showed 2q31-2q35 LOH, decreased protein expression and high cyclic nucleotide levels and cAMP-responsive element binding protein (CREB) phosphorylation. PDE11A codes for a dual-specificity PDE that is expressed in adrenal cortex and is partially inhibited by tadalafil and other PDE inhibitors; its germline inactivation is associated with adrenocortical hyperplasia, suggesting another means by which dysregulation of cAMP signaling causes endocrine tumors.     

DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice

Mitochondrial DNA (mtDNA) mutations are thought to have a causal role in many age-related pathologies. Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-directed DNA repair mechanism in mitochondria that is directly linked to the formation of mtDNA deletions. In addition, our results demonstrate that the rate at which mtDNA mutations reach phenotypic expression differs markedly among tissues, which may be an important factor in determining the tolerance of a tissue to random mitochondrial mutagenesis.     

Putting science over supposition in the arena of personalized genomics

Colleen McBride and colleagues argue that progress on a multifaceted research agenda is necessary to reap the full benefits and avoid the potential pitfalls of the emerging area of personalized genomics. They also outline one element of this agenda, the Multiplex Initiative, which has been underway since 2006.     

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.