Human health risk assessment: A case study involving heavy metal soil contamination after the flooding of the river Meuse during the winter of 1993-1994.

At the end of December 1993 and also at the end of January 1995, the river Meuse, one of the major rivers in Europe, flooded and river banks were inundated. We investigated the possible health risks of exposure to heavy metal concentrations in river bank soils resulting from the flooding of the river Meuse at the end of 1993. Soil and deposit samples and corresponding aerable and fodder crops were collected and analyzed for heavy metals. Although the soils of the floodplain of the river Meuse appeared severely polluted mainly by Cd and Zn, the heavy metal concentrations in the crops grown on these soils were within background ranges. Incidentally, the legal standard for Cd as endorsed by the Commodities Act was exceeded in wheat crops. The main exposure pathways for the general population were through the consumption of food crops grown on the river banks and through the direct ingestion of contaminated soils. For estimating potential human exposure in relation to soil pollution, we used a multiple pathway exposure model. For estimating the actual risk, we determined metal contents of vegetables grown in six experimental gardens. From this study, it can be concluded that there is a potential health risk for the river bank inhabitants as a consequence of Pb and Cd contaminations of the floodplain soils of the river Meuse, which are frequently inundated (averaged flooding frequency once every 2 years)

A Small Conductance Calcium-Activated K⁺ Channel in C. elegans, KCNL-2, Plays a Role in the Regulation of the Rate of Egg-Laying

In the nervous system of mice, small conductance calcium-activated potassium (SK) channels function to regulate neuronal excitability through the generation of a component of the medium afterhyperpolarization that follows action potentials. In humans, irregular action potential firing frequency underlies diseases such as ataxia, epilepsy, schizophrenia and Parkinson's disease. Due to the complexity of studying protein function in the mammalian nervous system, we sought to characterize an SK channel homologue, KCNL-2, in C. elegans, a genetically tractable system in which the lineage of individual neurons was mapped from their early developmental stages. Sequence analysis of the KCNL-2 protein reveals that the six transmembrane domains, the potassium-selective pore and the calmodulin binding domain are highly conserved with the mammalian homologues. We used widefield and confocal fluorescent imaging to show that a fusion construct of KCNL-2 with GFP in transgenic lines is expressed in the nervous system of C. elegans. We also show that a KCNL-2 null strain, kcnl-2(tm1885), demonstrates a mild egg-laying defective phenotype, a phenotype that is rescued in a KCNL-2-dependent manner. Conversely, we show that transgenic lines that overexpress KCNL-2 demonstrate a hyperactive egg-laying phenotype. In this study, we show that the vulva of transgenic hermaphrodites is highly innervated by neuronal processes and by the VC4 and VC5 neurons that express GFP-tagged KCNL-2. We propose that KCNL-2 functions in the nervous system of C. elegans to regulate the rate of egg-laying. © 2013 Chotoo et al

STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al

Measurement of the Negative Muon Anomalous Magnetic Moment to 0.7 ppm

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 parts per million (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement of the negative muon. The result a_mu= 11 659 214(8)(3) \times 10^{-10} (0.7 ppm), where the first uncertainty is statistical and the second is sytematic, is consistend with previous measurements of the anomaly for the positive and negative muon. The average for the muon anomaly a_{mu}(exp) = 11 659 208(6) \times 10^{-10} (0.5ppm).Comment: 4 pages, 4 figures, submitted to Physical Review Letters, revised to reflect referee comments. Text further revised to reflect additional referee comments and a corrected Fig. 3 replaces the older versio

Mode of Delivery and Asthma at School Age in 9 European Birth Cohorts

Evidence on the association between mode of delivery and asthma at school age is inconclusive. We assessed the associations between specific modes of delivery and asthma in children from 9 European birth cohorts that enrolled participants between 1996 and 2006. Cohort-specific crude and adjusted risk ratios for asthma at ages 5–9 years were calculated using Poisson regression models and pooled. A sensitivity analysis was carried out in children born at term to reduce confounding due to perinatal factors. The study included 67,613 participants. Cohortspecific rates of cesarean delivery varied from 9.4% to 37.5%. Cesarean delivery, as opposed to vaginal delivery, was associated with an increased risk of asthma (adjusted risk ratio (aRR) = 1.22, 95% confidence interval (CI): 1.02, 1.46). Compared with spontaneous vaginal delivery, the adjusted risk ratio was 1.33 (95% CI: 1.02, 1.75) for elective cesarean delivery, 1.07 (95% CI: 0.94, 1.22) for emergency cesarean delivery, and 0.97 (95% CI: 0.84, 1.12) for operative vaginal delivery. In children born at term, the associations were strengthened only for elective cesarean delivery (aRR = 1.49, 95% CI: 1.13, 1.97). The large sample size allowed analysis of the associations between specific modes of delivery and asthma at school age. The increased risk of asthma associated with elective cesarean delivery, especially among children born at term, is relevant in counteracting the increasing use of this procedure, which is often performed without a clear medical indication.This work was supported by the European Community’s Seventh Framework Programme (FP7/2009–2013) under a grant agreement (grant 241604) and by the University of Turin and the San Paolo Foundation (Turin, Italy). Data collection was funded and the study teams of all participating birth cohorts were supported by local and/or national research organizations

BicaudalD Actively Regulates Microtubule Motor Activity in Lipid Droplet Transport

A great deal of sub-cellular organelle positioning, and essentially all minus-ended organelle transport, depends on cytoplasmic dynein, but how dynein's function is regulated is not well understood. BicD is established to play a critical role in mediating dynein function-loss of BicD results in improperly localized nuclei, mRNA particles, and a dispersed Golgi apparatus-however exactly what BicD's role is remains unknown. Nonetheless, it is widely believed that BicD may act to tether dynein to cargos. Here we use a combination of biophysical and biochemical studies to investigate BicD's role in lipid droplet transport during Drosophila embryogenesis.Functional loss of BicD impairs the embryo's ability to control the net direction of droplet transport; the developmentally controlled reversal in transport is eliminated. We find that minimal BicD expression (near-BicD(null)) decreases the average run length of both plus and minus end directed microtubule (MT) based transport. A point mutation affecting the BicD N-terminus has very similar effects on transport during cellularization (phase II), but in phase III (gastrulation) motion actually appears better than in the wild-type.In contrast to a simple static tethering model of BicD function, or a role only in initial dynein recruitment to the cargo, our data uncovers a new dynamic role for BicD in actively regulating transport. Lipid droplets move bi-directionally, and our investigations demonstrate that BicD plays a critical-and temporally changing-role in balancing the relative contributions of plus-end and minus-end motors to control the net direction of transport. Our results suggest that while BicD might contribute to recruitment of dynein to the cargo it is not absolutely required for such dynein localization, and it clearly contributes to regulation, helping activation/inactivation of the motors

A 2-year prospective study of patient-relevant outcomes in patients operated on for knee osteoarthritis with tibial osteotomy

BACKGROUND: Tibial osteotomy is a treatment for younger and/or physically active patients suffering from uni-compartmental knee osteoarthritis. The open wedge osteotomy by the hemicallotasis technique includes the use of external fixation. The use of external fixation has several advantages, as early mobilization and the opportunity for optimal correction. However, the hemicallotasis technique has also been described as a cumbersome procedure for the patient. The aim of this study was to prospectively evaluate patient-relevant outcomes during the first 2 post-operative years. Especially the treatment period, during which external fixation was used, was closely monitored. METHODS: In an uncontrolled study, fifty-eight consecutive patients, 30 men and 28 women (mean age 54 years) were operated on by the hemicallotasis technique were evaluated with the patient-relevant outcome measure Knee injury and Osteoarthritis Outcome Score (KOOS) preoperatively, during the treatment with external fixation, one week after removal of the external fixation, at 6 months, and at one and two years postoperatively. RESULTS: At the 2-year postoperative follow-up, all subscales of the KOOS were improved (p < 0.001), mostly in pain (41–80 on a 0–100 worst to best scale) and knee-related quality of life (21–61 on a 0–100 worst to best scale), compared to the preoperative status. Significant improvements in pain and other symptoms, function of daily life and quality of life were seen already during the treatment period (mean 98 ± 18 days) with the external fixation. More demanding functions such as kneeling, squatting, jumping and running, were improved first after extraction of the external fixation device and the pins. CONCLUSION: Tibial osteotomy by the hemicallotasis technique yields large improvement in self-rated pain, function and quality of life, which persists over two years. Surprisingly, large improvements occurred already during the immediate post-operative period when the external fixation was still used

The evolution of galaxies from primeval irregulars to present-day ellipticals

The current understanding of galaxy formation is that it proceeds in a 'bottom up' way, with the formation of small clumps of gas and stars that merge hierarchically until giant galaxies are built up. The baryonic gas loses the thermal energy by radiative cooling and falls towards the centres of the new galaxies, while supernovae (SNe) blow gas out. Any realistic model therefore requires a proper treatment of these processes, but hitherto this has been far from satisfactory. Here we report an ultra-high-resolution simulation that follows evolution from the earliest stages of galaxy formation through the period of dynamical relaxation. The bubble structures of gas revealed in our simulation ($< 3\times10^8$ years) resemble closely the high-redshift Lyman $\alpha$ emitters (LAEs). After $10^9$ years these bodies are dominated by stellar continuum radiation and look like the Lyman break galaxies (LBGs) known as the high-redshift star-forming galaxies at which point the abundance of elements heavier than helium ("metallicity") appears to be solar. After $1.3\times10^{10}$ years, these galaxies resemble present-day ellipticals.Comment: 27 pages and 4 figures, Supplementary Information included, movie available on http://www.isc.senshu-u.ac.jp/~thj0613/natur