Interferon-free antiviral combination therapies without nucleosidic polymerase inhibitors

SummaryThe establishment of robust HCV cell culture systems and characterization of the viral life cycle provided the molecular basis for highly innovative, successful years in HCV drug development. With the identification of direct-acting antiviral agents (DAAs), such as NS3/4A protease inhibitors, NS5A replication complex inhibitors, nucleotide and non-nucleoside polymerase inhibitors, as well as host cell targeting agents, novel therapeutic strategies were established and competitively entered clinical testing. The first-in-class NS3/4A protease inhibitors telaprevir and boceprevir, approved in 2011, were recently outpaced by the pan-genotypic nucleotide polymerase inhibitor sofosbuvir that in combination with pegylated interferon and ribavirin, further shortens therapy durations and also offers the first interferon-free HCV treatment option. In the challenging race towards the goal of interferon-free HCV therapies, however, several oral DAA regimens without nucleotide polymerase inhibitors that combine a NS3/4A protease inhibitor, a NS5A inhibitor and/or a non-nucleoside polymerase inhibitor yielded competitive results. Second generation NS3/4A protease and NS5A inhibitors promise an improved genotypic coverage and a high resistance barrier. Results of novel DAA combination therapies without the backbone of a nucleotide polymerase inhibitor, as well as treatment strategies involving host targeting agents are reviewed herein

Effect of anions on dispersion of a kaolinitic soil clay: A combined study of dynamic light scattering and test tube experiments

Dispersion is an important issue for clay leaching in soils. In this study, effects of various anions (Cl-, SO42-, acetate, oxalate and citrate) on dispersion of a kaolinitic soil clay were determined at different pH values and ionic strengths by dynamic light scattering and test tube experiments. Adsorption of anions on clay samples was characterized by the zeta potential (ζ) in a pH range of 2 to 11. At a pH range between 2 and 6, the effects of different anions on decreasing ζ were obvious and followed the order oxalate>citrate>SO42->Cl->acetate, while fluctuated changes in ζ were observed at pH>6. Based on a comparison of hydrodynamic radii (rh) obtained from dynamic light scattering and of transmission of 50% (T50 values) from the test tube experiments, the ability of anions to facilitate the dispersion of the clay fraction followed the sequence of oxalate>citrate>acetate>SO42->Cl-. It implies that adsorption of anions on positively charged edge sites of kaolinite resulting in a decrease in ζ is a key factor for dispersion of the clay fraction. Also, the results suggested that the dynamic light scattering can be used in combination with the test tube experiments in order to evaluate the effect of anions on dispersion at broader ranges of pH, ionic strength and clay concentration.Vietnam National Foundation for Science & Technology Development/105.09-2010.0

Gebundene Wasserschichten an der Oberfläche von Smectit und der Einfluss auf den diffusiven Transport in Tonen

Der Einfluss von gebundenen Wasser-schichten auf den diffusiven Transport in Bentoniten wurde mit Hilfe von H2O?D2O Austauschexperimenten bei zwei verschie-denen Gesamtdichten und unter-schiedlicher Wassersättigung untersucht. Die Oberflächeneigenschaften des Bentonits wurden mit drei organischen Kationen (Hexadecylpyridinium (HDPy), Benze-thonium (BE) und Tetraphenylphosphonium (TPP)) modifiziert. Die Oberflächenladung und die damit zusammenhängende Benetzbarkeit haben einen deutlichen Einfluss auf die Menge des an der Oberfläche gebundenen H2O und damit auf das für die Diffusion nutzbare Porenvolumen und die Porennetzgeometrie. Die Probe mit der größten Hydrophobie und der geringsten Menge an gebundenen Wasserschichten zeigt den höchsten Deff mit einem Mittelwert von 7.59 x 10-11 m²/s bei Gesamtdichten von 1,0-1,5 g/cm³ und Wassersättigung der Probe. Die in diesem zeitsparenden Verfahren (durchschnittlich 22h) ermittelten Diffusionskoeffizienten zeigen darüber hinaus eine gute Übereinstimmung mit denen klassischer Diffusionsexperimente Der Bentonit weist einen mittleren Diffusionskoeffizienten von 2.44 x 10-11 m/s² bei Gesamtdichten von 1,0-1,5 g/cm³ und Wassersättigung der Probe auf

A new purge and trap headspace technique to analyze low volatile compounds from fluid inclusions of rocks and minerals

A new method for the analysis of trace gases from fluid inclusions of minerals has been developed. The purge and trap GC-MS system is based on the system described by Nolting et al. (1988) and was optimized for the analyses of halogenated volatile organic compounds (VOCs) having boiling points as low as -128. °C (carbon tetrafluoride).The sample preconcentration cold trap consists of a U-shaped glass lined steel tube (GLT™), that is immersed into a small liquid nitrogen Dewar vessel for cooling. A rapid desorption step heats up the preconcentration tube in <30s from -196°C to 200°C. The process is carried out by using a pressurized air stream to dissipate the liquid nitrogen followed by resistive heating of the trap. The design of the cold trap and the direct transfer of desorbed analytes onto the GC column via a deactivated capillary column retention gap made sample refocusing within the GC oven unnecessary. Furthermore, a special air-tight grinding device was developed in which samples ranging from soft halite (hardness 2, Mohs scale) to hard quartz (hardness 7) are effectively ground to average diameters of 1000nm or below, thereby releasing gases from fluid inclusions of minerals. The gases are then purged from the grinding chamber with a He carrier gas flow. The detection and quantitative determination of gases, such as SF6 and CF4 released from fluorites and CH3Cl from halite samples is demonstrated.DFG/FOR/76

Unsichtbar wirksam : Bodenmikroaggregate: kleine Strukturen mit großer Wirkung

In der Bodenforschung spielen Mikroaggregate eine besondere Rolle. Sie haben eine komplexe innere Architektur in der mikrobielle, biogeochemische und physikalische Prozesse in Wechselwirkung stehen, die bisher noch sehr wenig untersucht, aber von fundamentaler Bedeutung für die Funktionsfähigkeit von Böden sind. Wissenschaftler vom Institut für Bodenkunde versuchen daher, einen Beitrag zum mechanistischen Verständnis der Bildung und Funktion von Mikroaggregaten zu leisten

Encapsulation of Lead in Rice Phytoliths as a Possible Pollutant Source in Paddy Soils

Due to its serious health risks, lead (Pb) in rice, specifically its uptake, translocation, and accumulation mechanisms and its toxic effects have been studied intensively in recent years. However, it remains unclear about the role of phytolith, a siliceous structure in rice plants, in the storage and release kinetics of Pb in rice. This study aims at elucidating a possible encapsulation of Pb in the phytolith structure (phytPb), and identifying whether or not phytPb provides a source of Pb in soil, when returned to the field with the rice straw or in a related processed product such as ash from on-site burning. To date there has not been any specific work targeted at the determination of phytolith-associated heavy metals in general and phytPb in particular, and therefore this possible source of Pb in soils may have been overlooked. Phytoliths were included in a study of rice paddy soil and rice straw to demonstrate accumulation of phytolith and its associated phytPb in agricultural soils of the Red River Delta (Vietnam). The total content of Pb in rice straw samples was found to be up to 118mgkg−1,andthisPbsinkcanbecycledtoserveasanewPbsourceinsoils.ThefateofPbinricestraw might be directly related to open burning activity (a common practice in the Red River Delta), in which volatilization or sub-compartmentation in slagged phytolith appeared as controlled factors. This is supported by the findings from batch experiments for rice straw ash samples, in which release of Pb was low and a portion of Pb in rice straw were found to associate with phytolith structural organic matter. We also observed the presence of phytPbin aged phytolithfragmentswhichhadaccumulatedinthepaddyfieldsoil.HoweverthisPbpoolwas relativelylow(from7.8to34kgha−1)relativetoothersoilPbfractions.AsthethermaltreatmentsofPb-tainted rice straw resulted in losses of Pb via volatilization, open-field burning practices for Pb-contaminated rice straw is suggested as an environmental ris

Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis

Background and Aims: In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined. Methods: In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks). Results: Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001). Conclusions: Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis

The regulatory role of mine soil properties in the growth of revegetation plants in the post-mine landscape of East Kalimantan

The growth of revegetation plants in post-mining areas is determined by the mine soil quality, which strongly depends on the physical and chemical properties of the original soil. Visual observation of revegetation plants in two ex-coal mining areas in East Kalimantan, i.e. Lati and Sambarata sites, showed a clear difference in plants growth. This research aims to study the role of the physical and chemical properties of mine soil on the growth rate of revegetation plants so that it can be used to develop a sustainable ex-mining land reclamation strategy. The observation plots on each ex-mining land were grouped into (0–2), (2–4), (4–6), (6–8), (8–10), and (10–12) years since revegetation. In each group, soil sampling was carried out at a depth of 0–30 cm for analysis of soil physical and chemical properties. Observations were also made on the development of plant growth. The better revegetation plant growth at Sambarata site compared to those at Lati site was indicated by the composition of the stand structure, stem diameter, and plant height. Both sites have a similar texture, which is dominated by silt, and slightly higher bulk densities at Sambarata site compared to those at Lati site. Hence, not soil physical properties but soil chemistry played a regulatory role in the growth of revegetation plants. Here, the exchangeable cations at Sambarata site were dominated by Ca2+ and Mg2+, whereas those at Lati site were dominated by Al3+. Linked with a high base saturation, the pH, organic C, total N, and available P2O5 mine soil quality of the Sambarata site were more favourable for plants growth. Thus, in reclamation activities in post-mining areas, soil quality improvement using lime, rock phosphate, and compost is indispensable to increase soil fertility and establish fast revegetation. © 2022 The Author(s

Revegetation as a driver of chemical and physical soil property changes in a post-mining landscape of East Kalimantan: A chronosequence study

As a result of mixing soil materials from various natural soil horizons, mine soils generally have low organic C and total N content. In wet tropical climates where the vegetation is evergreen, we hypothesize that with the start of revegetation, the organic C and total N levels of the mine soils will recover rapidly and increase as the time since revegetation increases. The increase in organic C and total N content will have implications for changes in other soil chemical and physical properties. The development of mine soils in wet tropical climate conditions is so far rarely considered only. This study aims to determine changes in the physical and chemical properties of mine soils in the initial stages of formation triggered by the increasing time since revegetation. Soils from permanent observation plots in ex-coal mined sites divided by time since revegetation (0–12 years) were sampled together with an adjacent site with natural forest. Decisive soil physical and chemical properties were determined for the soils from 0 to 30 cm depth. With the increasing time since revegetation, there was a decrease in bulk density, and an increase in total soil porosity following a logarithmic equation. Linear changes with increasing time since revegetation were found for organic C, total N, and available P levels. The linear increase in organic C, total N, and available P levels, the logarithmic decrease in bulk density and the increase in total porosity with increasing time since revegetation suggest that these parameters are controlled by vegetation in the initial stages of mine soil development, while the polynomial changes in extractable P and K (25% HCl), CEC, exchangeable bases, base saturation percentage, and exchangeable Al over time suggest that these parameters can be assigned to processes independent of vegetation and are highly dependent on the composition of the original substrate. © 2022 The Author

Lichens Bite the Dust : A Bioweathering Scenario in the Atacama Desert

Bioweathering mediated by microorganisms plays a significant role in biogeochemical cycles on global scales over geological timescales. Single processes induced by specific taxa have been described but could rarely be demonstrated for complex communities that dominate whole landscapes. The recently discovered grit crust of the coastal Atacama Desert, which is a transitional community between a cryptogamic ground cover and a rock-bound lithic assemblage, offers the unique chance to elucidate various bioweathering processes that occur simultaneously. Here, we present a bioweathering scenario of this biocenosis including processes such as penetration of the lithomatrix, microbial responses to wet-dry cycles, alkalinolysis, enzyme activity, and mineral re-localization. Frequently occurring fog, for example, led to a volume increase of microorganisms and the lithomatrix. This, together with pH shifts and dust accumulation, consequently results in biophysical breakdown and the formation of a terrestrial protopedon, an initial stage of pedogenesis fueled by the grit crust. © 2020 The Author(s