Effect of enamel matrix derivative and parathyroid hormone on bone formation in standardized osseous defects: an experimental study in minipigs

Previous experimental studies have indicated that locally administered enamel matrix derivative (EMD) and parathyroid hormone (PTH) may have a stimulatory effect on bone formation. However, it is not clear if the positive effect of EMD is related to its effect on the periodontium as a whole or directly on the bone-forming cells. In addition, it is not known if the presentation of PTH by adding the amino acid sequence Arg-Gly-Asp (RGD) is essential for its osteopromotive effect. Local delivery of a bioactive substance at the right time and in the right concentration often constitutes a major challenge. Polyethylene glycol-based hydrogel (PEG) is a degradable vehicle developed for delivery of bioactive proteins. To enhance the mechanical stability of the PEG-bioactive substance complex, an osteoconductive bone substitute material is often needed.

Summer drought reduces total and litter-derived soil CO2 effluxes in temperate grassland - clues from a 13C litter addition experiment

Current climate change models predict significant changes in rainfall patterns across Europe. To explore the effect of drought on soil CO2 efflux (FSoil) and on the contribution of litter to FSoil we used rain shelters to simulate a summer drought (May to July 2007) in an intensively managed grassland in Switzerland by reducing annual precipitation by around 30% similar to the hot and dry year 2003 in Central Europe. We added 13C-depleted as well as unlabelled grass/clover litter to quantify the litter-derived CO2 efflux (FLitter). Soil CO2 efflux and the 13C/12C isotope ratio (δ13C) of the respired CO2 after litter addition were measured during the growing season 2007. Drought significantly decreased FSoil in our litter addition experiment by 59% and FLitter by 81% during the drought period itself (May to July), indicating that drought had a stronger effect on the CO2 release from litter than on the belowground-derived CO2 efflux (FBG, i.e. soil organic matter (SOM) and root respiration). Despite large bursts in respired CO2 induced by the rewetting after prolonged drought, drought also reduced FSoil and FLitter during the entire 13C measurement period (April to October) by 26% and 37%, respectively. Overall, our findings show that drought decreased FSoil and altered its seasonality and its sources. Thus, the C balance of temperate grassland soils respond sensitively to changes in precipitation, a factor that needs to be considered in regional models predicting the impact of climate change on ecosystems C balance.

Thermodynamics of the Hydroxyl Radical Addition to Isoprene

Oxidation of isoprene by the hydroxyl radical leads to tropospheric ozone formation. Consequently, a more complete understanding of this reaction could lead to better models of regional air quality, a better understanding of aerosol formation, and a better understanding of reaction kinetics and dynamics. The most common first step in the oxidation of isoprene is the formation of an adduct, with the hydroxyl radical adding to one of four unsaturated carbon atoms in isoprene. In this paper, we discuss how the initial conformations of isoprene, s-trans and s-gauche, influences the pathways to adduct formation. We explore the formation of pre-reactive complexes at low and high temperatures, which are often invoked to explain the negative temperature dependence of this reaction’s kinetics. We show that at higher temperatures the free energy surface indicates that a pre-reactive complex is unlikely, while at low temperatures the complex exists on two reaction pathways. The theoretical results show that at low temperatures all eight pathways possess negative reaction barriers, and reaction energies that range from −36.7 to −23.0 kcal·mol−1. At temperatures in the lower atmosphere, all eight pathways possess positive reaction barriers that range from 3.8 to 6.0 kcal·mol−1 and reaction energies that range from −28.8 to −14.4 kcal·mol−1.

Validation of a modified AVHRR aerosol optical depth retrieval algorithm over Central Europe

The Advanced Very High Resolution Radiometer (AVHRR) carried on board the National Oceanic and Atmospheric Administration (NOAA) and the Meteorological Operational Satellite (MetOp) polar orbiting satellites is the only instrument offering more than 25 years of satellite data to analyse aerosols on a daily basis. The present study assessed a modified AVHRR aerosol optical depth τa retrieval over land for Europe. The algorithm might also be applied to other parts of the world with similar surface characteristics like Europe, only the aerosol properties would have to be adapted to a new region. The initial approach used a relationship between Sun photometer measurements from the Aerosol Robotic Network (AERONET) and the satellite data to post-process the retrieved τa. Herein a quasi-stand-alone procedure, which is more suitable for the pre-AERONET era, is presented. In addition, the estimation of surface reflectance, the aerosol model, and other processing steps have been adapted. The method's cross-platform applicability was tested by validating τa from NOAA-17 and NOAA-18 AVHRR at 15 AERONET sites in Central Europe (40.5° N–50° N, 0° E–17° E) from August 2005 to December 2007. Furthermore, the accuracy of the AVHRR retrieval was related to products from two newer instruments, the Medium Resolution Imaging Spectrometer (MERIS) on board the Environmental Satellite (ENVISAT) and the Moderate Resolution Imaging Spectroradiometer (MODIS) on board Aqua/Terra. Considering the linear correlation coefficient R, the AVHRR results were similar to those of MERIS with even lower root mean square error RMSE. Not surprisingly, MODIS, with its high spectral coverage, gave the highest R and lowest RMSE. Regarding monthly averaged τa, the results were ambiguous. Focusing on small-scale structures, R was reduced for all sensors, whereas the RMSE solely for MERIS substantially increased. Regarding larger areas like Central Europe, the error statistics were similar to the individual match-ups. This was mainly explained with sampling issues. With the successful validation of AVHRR we are now able to concentrate on our large data archive dating back to 1985. This is a unique opportunity for both climate and air pollution studies over land surfaces.

Compressibility and Hydraulic Conductivity of Zeolite-Amended Soil-Bentonite Backfills

The effect of zeolite amendment for enhanced sorption capacity on the consolidation behavior and hydraulic conductivity, k, of a typical soil-bentonite (SB) backfill for vertical cutoff walls was evaluated via laboratory testing. The consolidation behavior and k of test specimens containing fine sand, 5.8 % (dry wt.) sodium bentonite, and 0, 2, 5, or 10 % (dry wt.) of one of three types of zeolite (clinoptilolite, chabazite-lower bed, or chabazite-upper bed) were measured using fixed-ring oedometers, and k also was measured on separate specimens using a flexible-wall permeameter. The results indicated that addition of a zeolite had little impact on either the consolidation behavior or the k of the backfill, regardless of the amount or type of zeolite. For example, the compression index, Cc, for the unamended backfill specimen was 0.24, whereas values of Cc for the zeolite amended specimens were in the range 0.19 ≤ Cc ≤ 0.23. Similarly, the k for the unamended specimen based on flexible-wall tests was 2.4 x 10-10 m/s, whereas values of k for zeolite amended specimens were in the range 1.2 x 10-10 ≤ k ≤ 3.9 x 10-10 m/s. The results of the study suggest that enhancing the sorption capacity of typical SB backfills via zeolite amendment is not likely to have a significant effect on the consolidation behavior or k of the backfill, provided that the amount of zeolite added is small (≤ 10 %).

High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade

Cutaneous T-cell lymphomas (CTCLs) are malignancies of skin-homing lymphoid cells, which have so far not been investigated thoroughly for common oncogenic mutations. We screened 90 biopsy specimens from CTCL patients (41 mycosis fungoides, 36 Sézary syndrome, and 13 non-mycosis fungoides/Sézary syndrome CTCL) for somatic mutations using OncoMap technology. We detected oncogenic mutations for the RAS pathway in 4 of 90 samples. One mycosis fungoides and one pleomorphic CTCL harbored a KRAS(G13D) mutation; one Sézary syndrome and one CD30(+) CTCL harbored a NRAS(Q61K) amino acid change. All mutations were found in stage IV patients (4 of 42) who showed significantly decreased overall survival compared with stage IV patients without mutations (P = .04). In addition, we detected a NRAS(Q61K) mutation in the CTCL cell line Hut78. Knockdown of NRAS by siRNA induced apoptosis in mutant Hut78 cells but not in CTCL cell lines lacking RAS mutations. The NRAS(Q61K) mutation sensitized Hut78 cells toward growth inhibition by the MEK inhibitors U0126, AZD6244, and PD0325901. Furthermore, we found that MEK inhibitors exclusively induce apoptosis in Hut78 cells. Taken together, we conclude that RAS mutations are rare events at a late stage of CTCL, and our preclinical results suggest that such late-stage patients profit from MEK inhibitors.

Addition of Zinc Sulfide Shells to Semiconducting Nanoparticles and its Effect on the Nanoparticle Fluorescence Emission Properties

The addition of a ZnS shell to CdSe and CdS quantum dot cores was explored using various methods. Spectrophotometry was used to assess the success of ZnS overcoating, which produces both an increase in overall fluorescence and decrease in particle size distribution. A new method was developed, involving preheating of the zinc and sulfide precursor solutions, resulting in CdSe(ZnS) particles with improved fluorescence and a more uniform shell coating from oleylamine-capped CdSe core particles.

Electroencephalographic topography measures of experienced utility

Economic theory distinguishes two concepts of utility: decision utility, objectively quantifiable by choices, and experienced utility, referring to the satisfaction by an obtainment. To date, experienced utility is typically measured with subjective ratings. This study intended to quantify experienced utility by global levels of neuronal activity. Neuronal activity was measured by means of electroencephalographic (EEG) responses to gain and omission of graded monetary rewards at the level of the EEG topography in human subjects. A novel analysis approach allowed approximating psychophysiological value functions for the experienced utility of monetary rewards. In addition, we identified the time windows of the event-related potentials (ERP) and the respective intracortical sources, in which variations in neuronal activity were significantly related to the value or valence of outcomes. Results indicate that value functions of experienced utility and regret disproportionally increase with monetary value, and thus contradict the compressing value functions of decision utility. The temporal pattern of outcome evaluation suggests an initial (∼250 ms) coarse evaluation regarding the valence, concurrent with a finer-grained evaluation of the value of gained rewards, whereas the evaluation of the value of omitted rewards emerges later. We hypothesize that this temporal double dissociation is explained by reward prediction errors. Finally, a late, yet unreported, reward-sensitive ERP topography (∼500 ms) was identified. The sources of these topographical covariations are estimated in the ventromedial prefrontal cortex, the medial frontal gyrus, the anterior and posterior cingulate cortex and the hippocampus/amygdala. The results provide important new evidence regarding “how,” “when,” and “where” the brain evaluates outcomes with different hedonic impact.

Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians

A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, the PNPLA3 single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79; P(genotype) = 1.2 × 10(-5) ; P(allelic) = 1.6 × 10(-6) ) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33; P(genotype) = 0.0085; P(allelic) = 0.0042). The latter, biochemically defined association was confirmed in an independent population-based cohort of at-risk drinkers with a median alcohol intake of 300 g/week (OR 4.75; P(genotype) = 0.040; P(allelic) = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele PNPLA3 rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (P(combined) = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele PNPLA3 rs738409(G) was estimated at 26.6%. CONCLUSION: Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians.

Retinal thickness in Parkinson's disease

BACKGROUND: Visual symptoms are common in Parkinson's disease with studies consistently demonstrating reductions in visual acuity, contrast sensitivity, colour and motion perception as well as alterations in electroretinogram latencies and amplitudes. Optical coherence tomography can examine retinal structure non-invasively and retinal thinning has been suggested as a potential biomarker for neurodegeneration in Parkinson's disease. Our aim was to examine the retinal thickness of a cohort of Parkinson's disease subjects (and age-matched controls) to establish the practical utility of optical coherence tomography in a representative older Parkinson's disease group. METHODS: Fifty-one established Parkinson's disease subjects and 25 healthy controls were subjected to ophthalmological assessment and optical coherence tomography (Zeiss Stratus 3000™) of macular thickness and volume and retinal nerve fibre thickness around the optic nerve head. Twenty four percent of control and 20% of Parkinson's disease subjects were excluded from final analysis due to co-morbid ocular pathology. Further data was excluded either due to poor tolerability of optical coherence tomography or poor quality scans. RESULTS: Despite a reduction in both visual acuity and contrast sensitivity in the residual evaluable Parkinson's disease cohort, we did not detect any differences between the two study groups for any measures of retinal thickness, in contrast to previously published work. CONCLUSIONS: In addition to technical problems inherent in the evaluation, the lack of difference between Parkinson's disease and healthy control subjects suggests longitudinal studies, employing newer techniques, will be required to define the role of optical coherence tomography as a potential diagnostic biomarker.

The airway epithelium: soldier in the fight against respiratory viruses

The airway epithelium acts as a frontline defense against respiratory viruses, not only as a physical barrier and through the mucociliary apparatus but also through its immunological functions. It initiates multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. The interaction between respiratory viruses and airway epithelial cells results in production of antiviral substances, including type I and III interferons, lactoferrin, β-defensins, and nitric oxide, and also in production of cytokines and chemokines, which recruit inflammatory cells and influence adaptive immunity. These defense mechanisms usually result in rapid virus clearance. However, respiratory viruses elaborate strategies to evade antiviral mechanisms and immune responses. They may disrupt epithelial integrity through cytotoxic effects, increasing paracellular permeability and damaging epithelial repair mechanisms. In addition, they can interfere with immune responses by blocking interferon pathways and by subverting protective inflammatory responses toward detrimental ones. Finally, by inducing overt mucus secretion and mucostasis and by paving the way for bacterial infections, they favor lung damage and further impair host antiviral mechanisms.