Fault lubrication during earthquakes

The determination of rock friction at seismic slip rates (about 1?m?s(-1)) is of paramount importance in earthquake mechanics, as fault friction controls the stress drop, the mechanical work and the frictional heat generated during slip. Given the difficulty in determining friction by seismological methods, elucidating constraints are derived from experimental studies. Here we review a large set of published and unpublished experiments (～300) performed in rotary shear apparatus at slip rates of 0.1-2.6?m?s(-1). The experiments indicate a significant decrease in friction (of up to one order of magnitude), which we term fault lubrication, both for cohesive (silicate-built, quartz-built and carbonate-built) rocks and non-cohesive rocks (clay-rich, anhydrite, gypsum and dolomite gouges) typical of crustal seismogenic sources. The available mechanical work and the associated temperature rise in the slipping zone trigger a number of physicochemical processes (gelification, decarbonation and dehydration reactions, melting and so on) whose products are responsible for fault lubrication. The similarity between (1) experimental and natural fault products and (2) mechanical work measures resulting from these laboratory experiments and seismological estimates suggests that it is reasonable to extrapolate experimental data to conditions typical of earthquake nucleation depths (7-15?km). It seems that faults are lubricated during earthquakes, irrespective of the fault rock composition and of the specific weakening mechanism involved.     

Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen

Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the top three causes of opportunistic human infections. A major factor in its prominence as a pathogen is its intrinsic resistance to antibiotics and disinfectants. Here we report the complete sequence of P. aeruginosa strain PAO1. At 6.3 million base pairs, this is the largest bacterial genome sequenced, and the sequence provides insights into the basis of the versatility and intrinsic drug resistance of P. aeruginosa. Consistent with its larger genome size and environmental adaptability, P. aeruginosa contains the highest proportion of regulatory genes observed for a bacterial genome and a large number of genes involved in the catabolism, transport and efflux of organic compounds as well as four potential chemotaxis systems. We propose that the size and complexity of the P. aeruginosa genome reflect an evolutionary adaptation permitting it to thrive in diverse environments and resist the effects of a variety of antimicrobial substances.     

A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome

Patients with a myelodysplastic syndrome (MDS) which has a risk of leukaemic change exhibit a variable clinical course. It has been suggested that the development of leukaemia in patients with MDS may be related to chromosomal abnormalities or genetic alterations: somatic mutation of the N-ras gene is now considered to be a critical step in the genetic basis of human leukaemogenesis. Here we report that DNAs of bone-marrow cells from three out of eight patients with MDS contained an activated N-ras oncogene, as detected by an in vivo selection assay in nude mice with transfected NIH 3T3 cells. Molecular analysis revealed the same single nucleotide substitution at codon 13 in all three transforming N-ras genes. Each of the three patients showed a progression of the disease and a resulting leukaemic change within the following year. Our observation of the mutation at codon 13 in leukaemic cell DNAs from all three cases suggests that activation of the N-ras gene is important in the development of leukaemia in some MDS cases.     

Regulation of myelopoiesis by proinflammatory cytokines in infectious diseases

Hematopoiesis is hierarchically orchestrated by a very small population of hematopoietic stem cells (HSCs) that reside in the bone-marrow niche and are tightly regulated to maintain homeostatic blood production. HSCs are predominantly quiescent, but they enter the cell cycle in response to inflammatory signals evoked by severe systemic infection or injury. Thus, hematopoietic stem and progenitor cells (HSPCs) can be activated by pathogen recognition receptors and proinflammatory cytokines to induce emergency myelopoiesis during infection. This emergency myelopoiesis counterbalances the loss of cells and generates lineage-restricted hematopoietic progenitors, eventually replenishing mature myeloid cells to control the infection. Controlled generation of such signals effectively augments host defense, but dysregulated stimulation by these signals is harmful to HSPCs. Such hematopoietic failure often results in blood disorders including chronic inflammatory diseases and hematological malignancies. Recently, we found that interleukin (IL)-27, one of the IL-6/IL-12 family cytokines, has a unique ability to directly act on HSCs and promote their expansion and differentiation into myeloid progenitors. This process resulted in enhanced production of neutrophils by emergency myelopoiesis during the blood-stage mouse malaria infection. In this review, we summarize recent advances in the regulation of myelopoiesis by proinflammatory cytokines including type I and II interferons, IL-6, IL-27, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and IL-1 in infectious diseases.     

L-threo-3,4-dihydroxyphenylserine, a noradrenaline precursor, inhibits dopamine release and metabolism in the rat striatum in vivo.

The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on dopamine (DA) release and metabolism in the striatum was studied in freely moving rats by intracerebral microdialysis techniques. The DA level as well as the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly decreased 140 min after the administration of L-threo-DOPS (50 mg/kg intraperitoneally). The results suggest that L-threo-DOPS inhibits the release and metabolism of DA in the striatum.     

L-threo-3,4-dihydroxyphenylserine,a noradrenaline precursor,inhibits dopamine release and metabolism in the rat striatum in vivo

The effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on dopamine (DA) release and metabolism in the striatum was studied in freely moving rats by intracerebral microdialysis techniques. The DA level as well as the levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly decreased 140 min after the administration of L-threo-DOPS (50 mg/kg intraperitoneally). The results suggest that L-threo-DOPS inhibits the release and metabolism of DA in the striatum.