Measurements of greenhouse gases and related tracers at Bialystok tall tower station in Poland

Quasi-continuous, in-situ measurements of atmospheric CO2, O2/N2, CH4, CO, N2O, and SF6 have been performed since August 2005 at the tall tower station near Bialystok, in Eastern Poland, from five heights up to 300 m. Besides the in-situ measurements, flask samples are filled approximately weekly and measured at Max-Planck Institute for Biogeochemistry for the same species and, in addition, for H2, Ar/N2 and the stable isotopes 13C and 18O in CO2. The in-situ measurement system was built based on commercially available analysers: a LiCor 7000 for CO2, a Sable Systems "Oxzilla" FC-2 for O2, and an Agilent 6890 gas chromatograph for CH4, CO, N2O and SF6. The system was optimized to run continuously with very little maintenance and to fulfill the precision requirements of the CHIOTTO project. The O2/N2 measurements in particular required special attention in terms of technical setup and quality assurance. The evaluation of the performance after more than three years of operation gave overall satisfactory results, proving that this setup is suitable for long term remote operation with little maintenance. The precision achieved for all species is within or close to the project requirements. The comparison between the in-situ and flask sample results, used to verify the accuracy of the in-situ measurements, showed no significant difference for CO2, O2/N2, CH4 and N2O, and a very small difference for SF6. The same comparison however revealed a statistically significant difference for CO, of about 6.5 ppb, for which the cause could not be fully explained. From more than three years of data, the main features at Bialystok have been characterized in terms of variability, trends, and seasonal and diurnal variations. CO2 and O2/N2 show large short term variability, and large diurnal signals during the warm seasons, which attenuate with the increase of sampling height. The trends calculated from this dataset, over the period August 2005 to December 2008, are 2.02±0.46 ppm/year for CO2 and -23.2±2.5 per meg/year for O2/N2. CH4, CO and N2O show also higher variability at the lower sampling levels, which in the case of CO is strongly seasonal. Diurnal variations in CH4, CO and N2O mole fractions can be observed during the warm season, due to the periodicity of vertical mixing combined with the diurnal cycle of anthropogenic emissions. We calculated increase rates of 10.1±4.4 ppb/year for CH4, (-8.3)±5.3 ppb/year for CO and 0.67±0.08 ppb/year for N2O. SF6 shows only few events, and generally no vertical gradients, which suggests that there are no significant local sources. A weak SF6 seasonal cycle has been detected, which most probably is due to the seasonality of atmospheric circulation. SF6 increased during the time of our measurement at an average rate of 0.29±0.01 ppt/year

In-situ measurements of oxygen, carbon monoxide and greenhouse gases from Ochsenkopf tall tower in Germany

We present 2.5 years (from June 2006 to December 2008) of in-situ measurements of CO2, O2, CH4, CO, N2O and SF6 mixing ratios sampled from 23, 90 and 163m above ground on the Ochsenkopf tower in the Fichtelgebirge range, Germany (50?0104900 N, 11?4803000 E, 1022ma.s.l.). In addition to the in-situ measurements, flask samples are taken at Ochsenkopf at approximately weekly intervals and are subsequently analysed for the mixing ratios of the same species, as well as H2, and the stable isotopes, ?13C, ?18O in CO2. The in-situ measurements of CO2 and O2 from 23m show substantial diurnal variations that are modulated by biospheric fluxes, combustion of fossil fuels, and by diurnal changes in the planetary boundary layer height. Measurements from 163m exhibit only very weak diurnal variability, as this height (1185ma.s.l.) is generally above the nocturnal boundary layer. CH4, CO, N2O and SF6 show little diurnal variation even at 23m owing to the absence of any significant diurnal change in the fluxes and the absence of any strong local sources or sinks. From the in-situ record, the seasonal cycles of the gas species have been characterized and the multi-annual trends determined. Because the record is short, the calculation of the trend is sensitive to inter-annual variations in the amplitudes of the seasonal cycles. However, for CH4 a significant change in the growth-rate was detected for 2006.5–2008.5 as compared with the global mean from 1999 to 2006 and is consistent with other recent observations of a renewed increasing global growth rate in CH4 since the beginning of 2007

A Small Molecule Inhibitor of Signal Peptide Peptidase Inhibits Plasmodium Development in the Liver and Decreases Malaria Severity

The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. LY411,575 was found to prevent Plasmodium's normal development in the liver, with an IC50 of approximately 80 nM, without affecting hepatocyte invasion by the parasite. In vivo results with a rodent model of malaria showed that LY411,575 decreases the parasite load in the liver and increases by 55% the resistance of mice to cerebral malaria, one of the most severe malaria-associated syndromes. Our data show that LY411,575 does not exert its effect via the Notch signaling pathway suggesting that it may interfere with Plasmodium development through an inhibition of the parasite's signal peptide peptidase. We therefore propose that selective signal peptide peptidase inhibitors could be potentially used for preventive treatment of malaria in humans

Antimetastatic gene expression profiles mediated by retinoic acid receptor beta 2 in MDA-MB-435 breast cancer cells

BACKGROUND: The retinoic acid receptor beta 2 (RARβ2) gene modulates proliferation and survival of cultured human breast cancer cells. Previously we showed that ectopic expression of RARβ2 in a mouse xenograft model prevented metastasis, even in the absence of the ligand, all-trans retinoic acid. We investigated both cultured cells and xenograft tumors in order to delineate the gene expression profiles responsible for an antimetastatic phenotype. METHODS: RNA from MDA-MB-435 human breast cancer cells transduced with RARβ2 or empty retroviral vector (LXSN) was analyzed using Agilent Human 1A Oligo microarrays. The one hundred probes with the greatest differential intensity (p < 0.004, jointly) were determined by selecting the top median log ratios from eight-paired microarrays. Validation of differences in expression was done using Northern blot analysis and quantitative RT-PCR (qRT-PCR). We determined expression of selected genes in xenograft tumors. RESULTS: RARβ2 cells exhibit gene profiles with overrepresentation of genes from Xq28 (p = 2 × 10(-8)), a cytogenetic region that contains a large portion of the cancer/testis antigen gene family. Other functions or factors impacted by the presence of exogenous RARβ2 include mediators of the immune response and transcriptional regulatory mechanisms. Thirteen of fifteen (87%) of the genes evaluated in xenograft tumors were consistent with differences we found in the cell cultures (p = 0.007). CONCLUSION: Antimetastatic RARβ2 signalling, direct or indirect, results in an elevation of expression for genes such as tumor-cell antigens (CTAG1 and CTAG2), those involved in innate immune response (e.g., RIG-I/DDX58), and tumor suppressor functions (e.g., TYRP1). Genes whose expression is diminished by RARβ2 signalling include cell adhesion functions (e.g, CD164) nutritional or metabolic processes (e.g., FABP6), and the transcription factor, JUN

Behavioural and Developmental Interventions for Autism Spectrum Disorder: A Clinical Systematic Review

Background: Much controversy exists regarding the clinical efficacy of behavioural and developmental interventions for improving the core symptoms of autism spectrum disorders (ASD). We conducted a systematic review to summarize the evidence on the effectiveness of behavioural and developmental interventions for ASD. Methods and Findings: Comprehensive searches were conducted in 22 electronic databases through May 2007. Further information was obtained through hand searching journals, searching reference lists, databases of theses and dissertations, and contacting experts in the field. Experimental and observational analytic studies were included if they were written in English and reported the efficacy of any behavioural or developmental intervention for individuals with ASD. Two independent reviewers made the final study selection, extracted data, and reached consensus on study quality. Results were summarized descriptively and, where possible, meta-analyses of the study results were conducted. One-hundred-and-one studies at predominantly high risk of bias that reported inconsistent results across various interventions were included in the review. Meta-analyses of three controlled clinical trials showed that Lovaas treatment was superior to special education on measures of adaptive behaviour, communication and interaction, comprehensive language, daily living skills, expressive language, overall intellectual functioning and socialization. High-intensity Lovaas was superior to low-intensity Lovaas on measures of intellectual functioning in two retrospective cohort studies. Pooling the results of two randomized controlle

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed