Loss of sphingosine kinase-1 in carcinoma cells increases formation of reactive oxygen species and sensitivity to doxorubicin-induced DNA damage

Sphingosine kinases (SK) catalyse the formation of sphingosine 1-phosphate, which is a key lipid mediator regulating cell responses such as proliferation, survival and migration. Here we have investigated the effect of targeted inhibition of SK-1 on cell damage and elucidated the mechanisms involved.

Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage

Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional overdose causes acute liver failure characterized by centrilobular hepatic necrosis with high morbidity and mortality. Although many molecular aspects of APAP-induced cell death have been described, no conclusive mechanism has been proposed. We recently identified TNF-related apoptosis-inducing ligand (TRAIL) and c-Jun kinase (JNK)-dependent activation of the pro-apoptotic Bcl-2 homolog Bim as an important apoptosis amplification pathway in hepatocytes. In this study, we, thus, investigated the role of TRAIL, c-JNK and Bim in APAP-induced liver damage. Our results demonstrate that TRAIL strongly synergizes with APAP in inducing cell death in hepatocyte-like cells lines and primary hepatocyte. Furthermore, we found that APAP strongly induces the expression of Bim in a c-JNK-dependent manner. Consequently, TRAIL- or Bim-deficient mice were substantially protected from APAP-induced liver damage. This study identifies the TRAIL-JNK-Bim axis as a novel target in the treatment of APAP-induced liver damage and substantiates its general role in hepatocyte death.

Applying erosion damage mapping to asses and quantify off-site effects of soil erosion in Switzerland

In order to fill existing knowledge gaps in the temporal and spatial distribution of soil erosion, its sources and causes, as well as in relation to its off-site impacts, erosion damage mapping of all visible erosion features was carried out at three study sites in Switzerland. The data illustrate that about one-quarter of the cultivated land was affected by water erosion. Observed mean annual soil loss rates are considered rather low (0.7–2.3 t/ha/y) compared to other European countries. However, substantial losses of >70 t/ha were recorded on individual plots. This paper focuses on the spatial aspects of soil erosion, by observing and comparing the study areas in a 1-year period from October 2005 to October 2006. The analyses illustrate that the sites differ considerably in average soil loss rates, but show similar patterns of off-site effects. In about one-third of the damaged plots an external source of surface runoff upslope contributed to the damage (run-on). Similarly, more than 50 per cent of the soil eroded on arable land deposited downslope on adjacent plots, roads, public/private infrastructure, etc., and 20 per cent of it reached open water bodies. Large amounts of eroded soil which deposit off-site, often related to slope depressions, are considered muddy floods and were frequently observed in Switzerland. Mapping, in conclusion, helps to sheds light on some of the important challenges of today, in particular: to comprehensively assess socioeconomic and ecological off-site effects of soil erosion, to attribute off-site impacts to on-site causes, and to raise awareness of all stakeholders involved, in order to improve ongoing discussions on policy formulation and implementation at the national and international levels.

The role of tissue damage in whiplash-associated disorders: discussion paper 1

Nonsystematic review of cervical spine lesions in whiplash-associated disorders (WAD).

Evaluation of Current Repair Criteria for Longitudinal Barrier with Crash Damage

To protect motorists and avoid tort liability, highway agencies expend considerable resources to repair damaged longitudinal barriers, such as w-beam guardrails. With limited funding available, though, highway agencies are unable to maintain all field-installed systems in the ideal as-built condition. Instead, these agencies focus on repairing only damage that has a detrimental effect on the safety performance of the barrier. The distinction between minor damage and more severe performance-altering damage, however, is not always clear. This paper presents a critical review of current United States (US) and Canadian criteria on whether to repair damaged longitudinal barrier. Barrier repair policies were obtained via comprehensive literature review and a survey of US and Canadian transportation agencies. In an analysis of the maintenance procedures of 40 US States and 8 Canadian transportation agencies, fewer than one-third of highway agencies were found to have quantitative measures to determine when barrier repair is warranted. In addition, no engineering basis for the current US barrier repair guidelines could be found. These findings underscore the importance of the development of quantitative barrier repair guidelines based on a strong technical foundation.

Oxidative damage to DNA related to survivorship and carotenoid-based sexual ornamentation in the common yellowthroat

Carotenoid-based sexual ornaments are hypothesized to be reliable signals of male quality, based on an allocation trade-off between the use of carotenoids as pigments and their use in antioxidant defence against reactive oxygen species. Carotenoids appear to be poor antioxidants in vivo, however, and it is not clear whether variation in ornament expression is correlated with measures of oxidative stress (OXS) under natural conditions. We used single-cell gel electrophoresis to assay oxidative damage to erythrocyte DNA in the common yellowthroat (Geothlypis trichas), a sexually dichromatic warbler in which sexual selection favours components of the males’ yellow ‘bib’. We found that the level of DNA damage sustained by males predicted their overwinter survivorship and was reflected in the quality of their plumage. Males with brighter yellow bibs showed lower levels of DNA damage, both during the year the plumage was sampled (such that yellow brightness signalled current OXS) and during the previous year (such that yellow brightness signalled past OXS). We suggest that carotenoid-based ornaments can convey information about OXS to prospective mates and that further work exploring the proximate mechanism(s) linking OXS to coloration is warranted.

Collateral Damage-Penetrating Head Injury and Orbital Injury: A Case Report

We report a case of an accidental death or potential suicide by revolver with subsequent injury of another person. A 44-year-old man shot himself in the head while manipulating his.38 caliber special revolver in the kitchen in the presence of his wife, standing approximately 1.5 m next to him. After passing through the husband's head, the lead round-nose bullet entered the region underneath his wife's left eye. When the bullet left the man's head, it retained the energy to penetrate the soft tissue at this distance, including the skin and thin bone plates like the orbital wall. Owing to the low energy of the projectile, the entry wound was of atypical in shape and without loss of tissue. Only a small line-resembling a cut-was externally visible. The man died in the hospital from his injuries; his wife suffered visual loss of her left eye.

Association between cam-type deformities and magnetic resonance imaging-detected structural hip damage: a cross-sectional study in young men

Objective Femoroacetabular impingement may be a risk factor for hip osteoarthritis in men. An underlying hip deformity of the cam type is common in asymptomatic men with nondysplastic hips. This study was undertaken to examine whether hip deformities of the cam type are associated with signs of hip abnormality, including labral lesions and articular cartilage damage, detectable on magnetic resonance imaging (MRI). Methods In this cross-sectional, population-based study in asymptomatic young men, 1,080 subjects underwent clinical examination and completed a self-report questionnaire. Of these subjects, 244 asymptomatic men with a mean age of 19.9 years underwent MRI. All MRIs were read for cam-type deformities, labral lesions, cartilage thickness, and impingement pits. The relationship between cam-type deformities and signs of joint damage were examined using logistic regression models adjusted for age and body mass index. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined. Results Sixty-seven definite cam-type deformities were detected. These deformities were associated with labral lesions (adjusted OR 2.77 [95% CI 1.31, 5.87]), impingement pits (adjusted OR 2.9 [95% CI 1.43, 5.93]), and labral deformities (adjusted OR 2.45 [95% CI 1.06, 5.66]). The adjusted mean difference in combined anterosuperior femoral and acetabular cartilage thickness was −0.19 mm (95% CI −0.41, 0.02) lower in those with cam-type deformities compared to those without. Conclusion Our findings indicate that the presence of a cam-type deformity is associated with MRI-detected hip damage in asymptomatic young men.