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Severe Disruption (severe + disruption)

Distribution by Scientific Domains

Life Sciences	50%
Business, Economics, Finance and Accounting	33%

Selected Abstracts

A variant of the Cockayne syndrome B gene ERCC6 confers risk of lung cancer,,

HUMAN MUTATION, Issue 1 2008
Zhongning Lin
Abstract Cockayne syndrome B protein (ERCC6) plays an essential role in DNA repair. However, the Cockayne syndrome caused by the ERCC6 defect has not been linked to cancer predisposition; likely due to the fact that cells with severe disruption of the ERCC6 function are sensitive to lesion-induced apoptosis, thus reducing the chance of tumorigenesis. The biological function and cancer susceptibility of a common variant rs3793784:C>G (c.,6530C>G) in the ERCC6 was examined. We show that the c.,6530C allele has lower binding affinity of Sp1 by EMSA and displays a lower transcriptional activity in vitro and in vivo. We then examined the contribution of this polymorphism to the risk of lung cancer in a case,control study with 1,000 cases and 1,000 controls. The case,control analysis revealed a 1.76-fold (P= × 10,9) excess risk of developing lung cancer for the c.,6530CC carriers compared with noncarriers. The c.,6530CC interacts with smoking to intensify lung cancer risk, with the odds ratio (OR)=9 for developing lung cancer among heavy smokers. Our data constituted strong evidence that ERCC6 rs3793784:C>G alters its transcriptional activity and may confer personalized susceptibility to lung cancer. Hum Mutat 29(1), 113,122, 2008. Published 2007, Wiley-Liss, Inc. [source]

Truck schedule recovery for solid waste collection in Porto Alegre, Brazil

INTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 5 2008
Jing-Quan Li
Abstract This paper considers a truck schedule recovery problem in the context of solid waste collection in the city of Porto Alegre, Brazil. When a truck on a scheduled trip breaks down, a backup truck needs to be selected to serve the cargo on that trip and other trucks might be rescheduled in order to gain the minimum operating and delay costs. The problem consists of designing, in the case of a severe disruption in a trip, new schedules taking into account the existing trucks in the system and a set of unfinished and not initiated collection trips, on which the trucks collect the solid waste in fixed routes and empty the loads in one of the several operational recycling facilities. The main objective is to minimize the total distances traveled and delay costs, as well as to obtain balanced assignments of truck unloads into the recycling facilities, due to the social benefits of the solid waste program. We modeled the problem as a mixed-integer linear problem and used CPLEX to solve it. Finally, computational experiments are conducted on real-world data. The results show that our approach successfully reduces the distances traveled and delays, simultaneously balancing the number of trucks unloading at each recycling facility, in comparison with the current manual strategy. [source]

AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunction

AGING CELL, Issue 4 2010
Subat Turdi
Summary Aging is associated with myocardial dysfunction although the underlying mechanism is unclear. AMPK, a key cellular fuel sensor for energy metabolism, is compromised with aging. This study examined the role of AMPK deficiency in aging-associated myocardial dysfunction. Young or old wild-type (WT) and transgenic mice with overexpression of a mutant AMPK ,2 subunit (kinase dead, KD) were used. AMPK , isoform activity, myocardial function and morphology were examined. DCF and JC-1 fluorescence probes were employed to quantify reactive oxygen species (ROS) and mitochondrial membrane potential (,,m), respectively. KD mice displayed significantly reduced ,2 but not ,1 AMPK isoform activity at both ages with a greater effect at old age. Aging itself decreased ,1 isoform activity. Cardiomyocyte contractile function, intracellular Ca2+ handling, and SERCA2a levels were compromised with aging, the effects of which were exacerbated by AMPK deficiency. H&E staining revealed cardiomyocyte hypertrophy with aging, which was more pronounced in KD mice. TEM micrographs displayed severe disruption of mitochondrial ultrastructure characterized by swollen, irregular shape and disrupted cristae in aged KD compared with WT mice. Aging enhanced ROS production and reduced ,,m, the effects of which were accentuated by AMPK deficiency. Immunoblotting data depicted unchanged Akt phosphorylation and a significant decrease in mitochondrial biogenesis cofactor PGC-1, in aged groups. AMPK deficiency but not aging decreased the phosphorylation of ACC and eNOS. Expression of membrane Glut4 and HSP90 was decreased in aged KD mice. Moreover, treatment of the AMPK activator metformin attenuated aging-induced cardiomyocyte contractile defects. Collectively, our data suggest a role for AMPK deficiency in aging-induced cardiac dysfunction possibly through disrupted mitochondrial function and ROS production. [source]

Sovereign Liquidity Crises: The Strategic Case For a Payments Standstill

THE ECONOMIC JOURNAL, Issue 460 2000
Marcus Miller
Is sovereign borrowing so different from corporate debt that there is no need for bankruptcy-style procedures to protect debtors? With the waiver of immunity, sovereign debtors who already face severe disruption from short-term creditors grabbing their currency reserves are also exposed to litigious creditors trying to seize what assets they can in a ,race of the vultures'. The lack of an orderly procedure for resolving sovereign liquidity crises means that the IMF is de facto forced to bail out countries in trouble. The strategic case for legalising standstills is to rescue the international financial system from this ,time consistency' trap. [source]

Genome-wide P -element screen for Drosophila synaptogenesis mutants

DEVELOPMENTAL NEUROBIOLOGY, Issue 4 2006
Faith L.W. Liebl
Abstract A molecular understanding of synaptogenesis is a critical step toward the goal of understanding how brains "wire themselves up," and then "rewire" during development and experience. Recent genomic and molecular advances have made it possible to study synaptogenesis on a genomic scale. Here, we describe the results of a screen for genes involved in formation and development of the glutamatergic Drosophila neuromuscular junction (NMJ). We screened 2185 P -element transposon mutants representing insertions in ,16% of the entire Drosophila genome. We first identified recessive lethal mutants, based on the hypothesis that mutations causing severe disruptions in synaptogenesis are likely to be lethal. Two hundred twenty (10%) of all insertions were homozygous lethal. Two hundred five (93%) of these lethal mutants developed at least through late embryogenesis and formed neuromusculature. We examined embryonic/larval NMJs in 202 of these homozygous mutants using immunocytochemistry and confocal microscopy. We identified and classified 88 mutants with altered NMJ morphology. Insertion loci in these mutants encode several different types of proteins, including ATP- and GTPases, cytoskeletal regulators, cell adhesion molecules, kinases, phosphatases, RNA regulators, regulators of protein formation, transcription factors, and transporters. Thirteen percent of insertions are in genes that encode proteins of novel or unknown function. Complementation tests and RT-PCR assays suggest that approximately 51% of the insertion lines carry background mutations. Our results reveal that synaptogenesis requires the coordinated action of many different types of proteins,perhaps as much as 44% of the entire genome,and that transposon mutageneses carry important caveats that must be respected when interpreting results generated using this method. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]

History of marine biodiversity

GEOLOGICAL JOURNAL, Issue 3-4 2001
Peter M. Sheehan
Abstract During the Phanerozoic, three steps of increasing diversity each had a unique Evolutionary Fauna (EF). During each EF, there were geologically long intervals of community stasis referred to as Ecological Evolutionary Units (EEUs). These intervals were characterized by communities composed of incumbent faunas that dominated particular habitats. Niches that were already occupied by incumbents were seldom invaded by new taxa, and the resilience of the incumbents to new competitors resulted in the long interval stasis. Most EEUs were terminated by extinction events that were caused by severe disruptions of the physical environment such as glaciations and extraterrestrial impacts. During mass extinctions many niches were vacated when incumbents were eliminated. Mass extinctions were followed by recovery intervals lasting on the order of 5 million years during which many surviving clades evolved adaptations which allowed them to move into vacated niches. New incumbents were established during these recovery intervals, and the next EEU began. In many ways, the recovery intervals resemble times when organisms invaded previously unoccupied ecospace, such as the emergence of life on land or the progressive filling of previously unoccupied habitats such as deep-burrowing and high epifaunal tiers that were colonized during the Palaeozoic. The recognition of long intervals of ecological stasis and the importance of physical disruptions in clearing incumbents is forcing revision of the traditional evolutionary viewpoint. The idea that most evolutionary change was accomplished very gradually by competition between organisms and by becoming better adapted to a relatively stable environment is being replaced by a recognition that major morphological and synecological changes tend to occur very rapidly and at times when there are few established competitors. Copyright © 2001 John Wiley & Sons, Ltd. [source]