Sequence variations in alleles of the avirulence gene avrPphE.R2 from Pseudomonas syringae pv. phaseolicola lead to loss of recognition of the AvrPphE protein within bean cells and a gain in cultivar-specific virulence

The bean halo blight pathogen, Pseudomonas syringae pv. phaseolicola ( Psph ), is differentiated into nine races based on the presence or absence of five avirulence ( avr ) genes in the bacterium, which interact with corresponding resistance genes, R1–R5 , in Phaseolus vulgaris . The resistance gene R2 is matched by avrPphE , which is located adjacent to the cluster of hrp genes that are required for pathogenicity of Psph . Although only races 2, 4, 5 and 7 are avirulent on cultivars with R2 (inducing the hypersensitive response; HR), homologues of avrPphE are present in all races of Psph . DNA sequencing of avrPphE alleles from races of Psph has demonstrated two routes to virulence: via single basepair changes conferring amino acid substitutions in races 1, 3, 6 and 9 and an insertion of 104 bp in the allele in race 8. We have demonstrated that these base changes are responsible for the difference between virulence and avirulence by generating transconjugants of a virulent race harbouring plasmids expressing the various alleles of avrPphE. Agrobacterium tumefaciens -directed expression of avrPphE from race 4 in bean leaves induced the HR in a resistance gene-specific manner, suggesting that the AvrPphE protein is alone required for HR induction and is recognized within the plant cell. The allele from race 6, which is inactive if expressed in Psph , elicited a weak HR if expressed in planta , whereas the allele from race 1 did not. Our results suggest that the affinity of interaction between AvrPphE homologues and an unknown plant receptor mediates the severity of the plant's response. Mutation of avrPphE alleles did not affect the ability to colonize bean from a low level of inoculum. The avirulence gene avrPphB , which matches the R3 resistance gene, also caused a gene-specific HR following expression in the plant after delivery by A. tumefaciens .     

The Network RamDisk: Using remote memory on heterogeneous NOWs

Efficient data storage, a major concern in the modern computer industry, is mostly provided today by traditional magnetic disks. However, the cost of a disk transfer (measured in processor cycles) continues to increase with time, making disk accesses increasingly expensive. In this paper we describe the design, implementation and evaluation of a Network RamDisk device that uses main memory of remote workstations as a fasterthandisk storage device. In our study we propose various reliability policies, making the device tolerant to single workstation crashes. We show that the Network RamDisk is portable, flexible, and can operate under any of the existing Unix file systems. The Network RamDisk has been implemented both on the Linux and the Digital Unix operating systems, as a block device driver without any modifications to the kernel code. Using several real applications and benchmarks, we measure the performance of the Network RamDisk over an Ethernet and an ATM network, and find it to be usually four to eight times better than the magnetic disk. In one benchmark, our system was two orders of magnitude faster than the disk. We believe that a Network RamDisk can be efficiently used to provide reliable lowlatency access to files that would otherwise be stored on magnetic disks.     

Practice reduces motor unit discharge variability in a hand muscle and improves manual dexterity in old adults.

A steadiness-improving intervention was used to determine the contribution of variability in motor unit discharge rate to the fluctuations in index finger acceleration and manual dexterity in older adults. Ten healthy and sedentary old adults (age 72.9 +/- 5.8 yr; 5 men) participated in the study involving abduction of the left index finger. Single motor unit activity was recorded in the first dorsal interosseus muscle before, after 2 wk of light-load training (10% maximal load), and after 4 wk of heavy-load training (70% maximal load). As expected, the light-load training was effective in reducing the fluctuations in index finger acceleration during slow shortening (0.25 +/- 0.12 to 0.13 +/- 0.08 m/s(2)) and lengthening contractions (0.29 +/- 0.10 to 0.14 +/- 0.06 m/s(2)). Along with the decline in the magnitude of the fluctuations, there was a parallel decrease in the coefficient of variation for discharge rate during both contraction types (33.8 +/- 6.8 to 25.0 +/- 5.9%). The heavy-load training did not further improve either the fluctuations in acceleration or discharge rate variability. Furthermore, the manual dexterity of the left hand improved significantly with training (Purdue pegboard test: 11 +/- 3 to 14 +/- 1 pegs). Bivariate correlations indicated that the reduction in fluctuations in motor output during shortening (r(2) = 0.24) and lengthening (r(2) = 0.14) contractions and improvement in manual dexterity (r(2) = 0.26) was directly associated with a decline in motor unit discharge rate variability. There was a strong association between the fluctuations in motor output and manual dexterity (r(2) = 0.56). These results indicate that practice of a simple finger task was accompanied by a reduction in the discharge rate variability of motor units, a decrease in the fluctuations in motor output of a hand muscle, and an improvement in the manual dexterity of older adults.     

A study on the compliance of a right coronary artery and its impact on wall shear stress

A computational model incorporating physiological motion and uniform transient wall deformation of a branchless right coronary artery (RCA) was developed to assess the influence of artery compliance on wall shear stress (WSS). Arterial geometry and deformation were derived from modern medical imaging techniques, whereas the blood flow was solved numerically employing a moving-grid approach using a well-validated in-house finite element code. The simulation results indicate that artery compliance affects the WSS in the RCA heterogeneously, with the distal region mostly experiencing these effects. Under physiological inflow conditions, coronary compliance contributed to phase changes in the WSS time history, without affecting the temporal gradient of the local WSS nor the bounds of the WSS magnitude. Compliance does not cause considerable changes to the topology of WSS vector patterns nor to the localization of WSS minima along the RCA. We conclude that compliance is not an important factor affecting local hemodynamics in the proximal region of the RCA while the influence of compliance in the distal region needs to be evaluated in conjunction with the outflow to the myocardium through the major branches of the RCA.     

Trimetazidine protects low-density lipoproteins from oxidation and cultured cells exposed to H2O2 from DNA damage

Trimetazidine is a well-established anti-ischemic drug, which has been used for long time in the treatment of pathological conditions related with the generation of reactive oxygen species. However, although extensively studied, its molecular mode of action remains largely unknown. In the present study, the ability of trimetazidine to protect low-density lipoproteins (LDL) from oxidation and cultured cells from H₂O₂-induced DNA damage was investigated. Trimetazidine, tested at concentrations 0.02 to 2.20 mM, was shown to offer significant protection to LDL exposed to three different oxidizing systems, namely copper, Fe/ascorbate, and met-myoglobin/H₂O₂. The oxidizability of LDL was estimated by measuring, (i) the lag period, (ii) the maximal rate of conjugated diene formation, (iii) the total amount of conjugated dienes formed, (iv) the electrophoretic migration of LDL protein in agarose gels (REM), and (v) the inactivation of the enzyme PAF-acetylhydrolase present in LDL. In addition, the presence of trimetazidine decreased considerably the DNA damage in H₂O₂-exposed Jurkat cells in culture. H₂O₂ was continuously generated by the action of glucose oxidase at a rate of 11.8 ± 1.5 μM per min (60 ng enzyme per 100 μl), and DNA damage was assessed by the single cell gel electrophoresis assay (also called comet assay). The protection offered by trimetazidine in this system (about 30% at best) was transient, indicating modification of this agent during its action. These results indicate that trimetazidine can modulate the action of oxidizing agents in different systems. Although its mode of action is not clarified, the possibility that it acts as a lipid barrier permeable transition metal chelator is considered.     

Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome

The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1) and discharge (group B2) and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1beta and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1beta, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.