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The aim of this work was to identify, which of the known ionic liquids used within the technical area, primarily as a lubricant, would also be appropriate for use as a hydraulic fluid. In this context, their suitability has been proved based on experimental research with respect to the appropriate physical and chemical properties as required for mineral based hydraulic fluid. Primary aim of the research was to determine the ability of ILs to protect against corrosion, which is one of the important factors in choosing an ionic liquid. The results show that, despite excellent lubricating properties, certain ILs fail on this corrosion test. Except the corrosion protection performance of the basic hydraulic components parts, e.g. hydraulic pumps and valves, in the foreground was their compatibility with other materials used within other parts of hydraulic system, e.g. coating of the hydraulic tank and the filter material. For this purpose standard tests methods for mineral based hydraulic oils have been used, supplemented with non-standard tests, carried out at the same conditions as they occur during the operation of the hydraulic system. [ABSTRACT FROM AUTHOR]

A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMPactivated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1(G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK 2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease. [ABSTRACT FROM AUTHOR]

Background and objectives: Aortic ischaemia and reperfusion may induce pulmonary sequestration of neutrophil granulocytes. Preconditioning and postconditioning with volatile anaesthetics confer protection against reperfusion injury in various organs, such as heart, kidneys or brain. We tested the hypothesis that pre- or post- conditioning with Sevoflurane attenuates pulmonary neutrophil accumulation after ischaemia/reperfusion injury of the aorta. Methods: Anaesthetized and mechanically ventilated Wistar rats underwent laparotomy and were randomly assigned to one of the following groups: Sham (n = 10), ischaemia!reperfusion (n 8, lower body ischaemia by clamping of the infrarenal aorta for 2 h followed by 3 h of reperfusion), preconditioning (n = 10, 2.0% Sevoflurane administered over 30 mm prior to ischaemia) and postconditioning (n = 9, 2.0% Sevoflurane during reperfusion). Following reperfusion, the lungs were removed for microscopic determination of neutrophil accumulation. Results: Ischaemia/reperfusion induced a significant increase in pulmonary neutrophil accum- ulation (mean ± SD, 29.9 ± 7.4 vs. 15.8 ± 6.6 neutrophils per microscopic field in ischaemia/reperfusion vs. Sham, respectively, P < 0.001). Sevoflurane preconditioning resulted in a lower neutrophil count (20.3 ± 7.1 neutrophils, P < 0.001 vs. ischaemialreperfusion), while postconditioning showed no effects (25.8 ± 9.8 neutrophils vs. ischaemialreperfusion, not significant). Conclusions: Preconditioning, but not postconditioning, with Sevoflurane reduces pulmonary neutrophil accumulation after ischaemiaireperfusion injury of the lower body. Since neutrophil accumulation plays a major role in the pathophysiology of acute lung injury, our data suggest a protective effect of Sevoflurane preconditioning on remote pulmonary ischaemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Nephrogenic systemic fibrosis (NSF) describes a characteristic fibrosing disorder which typically presents with indurated plaques on the trunk and extremities of patients with advanced renal disease. We present a case of biopsy-confirmed NSF in a patient with severe acute kidney injury with no prior history of renal disease. A 64-year-old man with an acute and severe decrease in glomerular filtration rate underwent magnetic resonance imaging studies with gadolinium contrast (Omniscan™) and subsequently developed NSF. His renal disease had normalized at the time his skin disease developed. Skin biopsies revealed findings of NSF and scanning electron microscopy with energy-dispersive X-ray spectroscopy confirmed insoluble gadolinium within lesional tissue. [ABSTRACT FROM AUTHOR]

Bladder carcinomas frequently show extensive deletions of chromosomes 9p and/or 9q, potentially including the loci of the Fanconi anemia (FA) genes FANCC and FANCG. FA is a rare recessive disease due to defects in anyone of 13 FANC genes manifesting with genetic instability and increased risk of neoplasia. FA cells are hypersensitive towards DNA crosslinking agents such as mitomycin C and cisplatin that are commonly employed in the chemotherapy of bladder cancers. These observations suggest the possibility of disruption of the FA/BRCA DNA repair pathway in bladder tumors. However, mutations in FANCC or FANCG could not be detected in any of 23 bladder carcinoma cell lines and ten surgical tumor specimens by LOH analysis or by FANCD2 immunoblotting assessing proficiency of the pathway. Only a single cell line, BFTC909, proved defective for FANCD2 monoubiquitination and was highly sensitive towards mitomycin C. This increased sensitivity was restored specifically by transfer of the FANCF gene. Sequencing of FANCF in BFTC909 failed to identify mutations, but methylation of cytosine residues in the FANCF promoter region was demonstrated by methylation-specific PCR, HpaII restriction and bisulfite DNA sequencing. Methylation-specific PCR uncovered only a single instance of FANCF promoter hypermethylation in surgical specimens of further 41 bladder carcinomas. These low proportions suggest that in contrast to other types of tumors silencing of FANCF is a rare event in bladder cancer and that an intact FA/BRCA pathway might be advantageous for tumor progression. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and objectives: During partial liquid ventilation perfluorocarbons are instilled into the airways from where they subsequently evaporate via the bronchial system. This process is influenced by multiple factors, such as the vapour pressure of the perfluorocarbons, the instilled volume, intrapulmonary perfluorocarbon distribution, postural positioning and ventilatory settings. In our study we compared the effects of open and closed breathing systems, a heat-and-moisture-exchanger and a sodalime absorber on perfluorocarbon evaporation during partial liquid ventilation. Methods: Isolated rat lungs were suspended from a force transducer. After intratracheal perfluorocarbon instillation (10 mL kg-1) the lungs were either ventilated with an open breathing system (n = 6), a closed breathing system (n = 6), an open breathing system with an integrated heat-and-moisture-exchanger (n = 6), an open breathing system with an integrated sodalime absorber (n = 6), or a closed breathing system with an integrated heat-and-moisture-exchanger and a sodalime absorber (n = 6). Evaporative perfluorocarbon elimination was determined gravimetrically. Results: When compared to the elimination half-life in an open breathing system (1.2 ± 0.07 h), elimination half-life was longer with a closed system (6.4 ± 0.9h, P < 0.01), a sodalime absorber (5.0 ± 0.6 h, P < 0.01) or a heat-and-moisture-exchanger (4.5 ± 0.8 h, P < 0.01). The combination of all three methods (7.1 ± 0.8 h) showed no significant additional effects (P > 0.05) when compared to a closed system. Conclusions: Evaporative perfluorocarbon loss can be reduced effectively with closed breathing systems, followed by the use of sodalime absorbers and heat-and-moisture-exchangers. [ABSTRACT FROM AUTHOR]

Background and objectives: Salt-water aspiration results in pulmonary oedema and hypoxia. We tested the hypothesis that partial liquid ventilation has beneficial effects on gas exchange and rate of survival in acute and extended saltwater-induced lung injury. Methods: Anaesthetized, ventilated rats (tidal volume 6 mL kg-1, PEEP 5 cmH2O) received a tracheal salt-water instillation (3%, 8 mLkg-1 body weight) and were randomly assigned to three groups (n = 10 per group). While lungs of Group 1 were gas-ventilated, lungs of Group 2 received a single perfluorocarbon instillation (30 min after the injury, 5 mLkg-1 perfluorocarbon) and lungs of Group 3 received an additional continuous perfluorocarbon application into the treachea (5 mLkg-1h-1). Arterial blood gases were measured with an intravascular blood gas sensor. Results: Salt-water instillation resulted in a marked decrease in PaO2 values within 30min (from 432 ± 65 to 83 ± 40 mmHg, F1O2 = 1.0, P « 0.01). Arterial oxygenation improved in all three groups irrespective of treatment. We observed no significant differences between groups in peak PaO2 and PaCO2 values. Conclusions: Our results suggest that partial liquid ventilation has no additional beneficial effects on gas exchange after life-threatening salt water-induced lung injury when compared to conventional gas ventilation with positive end-expiratory pressure. [ABSTRACT FROM AUTHOR]

Biallelic mutations in BRCA2/FANCD1 were recently recognized as a rare cause of Fanconi anemia (FA). Using immunodetection with an antiserum directed against the carboxyterminus of the BRCA2 protein, we screened 38 lymphoid cell lines from FA patients whom we could not previously assign, via retroviral complementation analysis, to any of six known FA complementation groups (FA-A, -C, -D2, -E, -F, or -G). Three of these 38 cell lines lacked the 380-kDa BRCA2 signal on immunoblots. DNA sequencing showed biallelic compound and truncating mutations in two of the immuno-negative cell lines, whereas a monoallelic frameshift mutation and an amino acid substitution were detected in the third cell line. Our data show that less than 10% of unassigned FA cell lines harbor truncating mutations in BRCA2/FANCD1. This finding strongly suggests the existence of (an) additional, as yet unknown FA gene(s). Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal motor neuron disease. Diagnosis typically occurs in the fifth decade of life and the disease progresses rapidly leading to death within ~ 2–5 years of symptomatic onset. There is no cure, and the few available treatments offer only a modest extension in patient survival. A protein central to ALS is the nuclear RNA/DNA-binding protein, TDP-43. In > 95% of ALS patients, TDP-43 is cleared from the nucleus and forms phosphorylated protein aggregates in the cytoplasm of affected neurons and glia. We recently defined that poly(ADP-ribose) (PAR) activity regulates TDP-43-associated toxicity. PAR is a posttranslational modification that is attached to target proteins by PAR polymerases (PARPs). PARP-1 and PARP-2 are the major enzymes that are active in the nucleus. Here, we uncovered that the motor neurons of the ALS spinal cord were associated with elevated nuclear PAR, suggesting elevated PARP activity. Veliparib, a small-molecule inhibitor of nuclear PARP-1/2, mitigated the formation of cytoplasmic TDP-43 aggregates in mammalian cells. In primary spinal-cord cultures from rat, Veliparib also inhibited TDP-43-associated neuronal death. These studies uncover that PAR activity is misregulated in the ALS spinal cord, and a small-molecular inhibitor of PARP-1/2 activity may have therapeutic potential in the treatment of ALS and related disorders associated with abnormal TDP-43 homeostasis. [ABSTRACT FROM AUTHOR]

An abstract of the article "Novel Borohydride-Based Ionic Liquids as Hydrogen Carrier," by C. Grimmer and colleagues is presented.

Provides supplementary information on topics related to genetics, which appeared in the November 2005 issue of “Nature Genetics.”