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Background: Chronic hepatitis C virus (HCV) infections are causally linked with metabolic comorbidities such as insulin resistance, hepatic steatosis, and dyslipidemia. However, the clinical impact of HCV eradication achieved by direct-acting antivirals (DAAs) on glucose and lipid homeostasis is still controversial. The study aimed to prospectively investigate whether antiviral therapy of HCV with DAAs alters glucose and lipid parameters. Methods: 50 patients with chronic HCV who were treated with DAAs were screened, and 49 were enrolled in the study. Biochemical and virological data, as well as noninvasive liver fibrosis parameters, were prospectively collected at baseline, at the end of treatment (EOT) and 12 and 24 weeks post-treatment. Results: 45 of 46 patients achieved sustained virologic response (SVR). The prevalence of insulin resistance (HOMA-IR) after HCV clearance was significantly lower, compared to baseline (5.3 ± 6.1 to 2.5 ± 1.9, p < 0.001), which is primarily attributable to a significant decrease of fasting insulin levels (18.9 ± 17.3 to 11.7 ± 8.7; p = 0.002). In contrast to that, HCV eradication resulted in a significant increase in cholesterol levels (total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein (HDL-C) levels) and Controlled Attenuated Score (CAP), although BMI did not significantly change over time (p = 0.95). Moreover, HOMA-IR correlated significantly with noninvasive liver fibrosis measurements at baseline und during follow-up (TE: r = 0.45; p = 0.003, pSWE: r = 0.35; p = 0.02, APRI: r = 0.44; p = 0.003, FIB-4: r = 0.41; p < 0.001). Conclusion: Viral eradication following DAA therapy may have beneficial effects on glucose homeostasis, whereas lipid profile seems to be worsened.
In optogenetics, rhodopsins were established as light-driven tools to manipulate neuronal activity. However, during long-term photostimulation using channelrhodopsin (ChR), desensitization can reduce effects. Furthermore, requirement for continuous presence of the chromophore all-trans retinal (ATR) in model systems lacking sufficient endogenous concentrations limits its applicability. We tested known, and engineered and characterized new variants of de- and hyperpolarizing rhodopsins in Caenorhabditis elegans. ChR2 variants combined previously described point mutations that may synergize to enable prolonged stimulation. Following brief light pulses ChR2(C128S;H134R) induced muscle activation for minutes or even for hours (‘Quint’: ChR2(C128S;L132C;H134R;D156A;T159C)), thus featuring longer open state lifetime than previously described variants. Furthermore, stability after ATR removal was increased compared to the step-function opsin ChR2(C128S). The double mutants C128S;H134R and H134R;D156C enabled increased effects during repetitive stimulation. We also tested new hyperpolarizers (ACR1, ACR2, ACR1(C102A), ZipACR). Particularly ACR1 and ACR2 showed strong effects in behavioral assays and very large currents with fast kinetics. In sum, we introduce highly light-sensitive optogenetic tools, bypassing previous shortcomings, and thus constituting new tools that feature high effectiveness and fast kinetics, allowing better repetitive stimulation or investigating prolonged neuronal activity states in C. elegans and, possibly, other systems.
Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Research suggests that the cumulative impact of common alleles with small effects explains only around 25–38% of the phenotypic variance for BD. A plausible hypothesis therefore is that rare, high penetrance variants may contribute to BD risk. The present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members. After correction for multiple testing, no significant increase in polygenic risk scores for common, BD-associated genetic variants was found in BD cases compared to healthy relatives. Exome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported previously as a genome-wide significant risk gene for schizophrenia. The present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks.
This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1.
This study presents a taxonomic update of the Tetramorium weitzeckeri species group.
Tetramorium mpala sp. nov. is described from Laikipia, Kenya, and placed in the T. weitzeckeri species complex. In addition, we also provide an illustrated identification key to the three species complexes of the T. weitzeckeri species group, and an updated illustrated identification key to the species of the T. weitzeckeri species complex.
In non-hadronic axion models, which have a tree-level axion-electron interaction, the Sun produces a strong axion flux by bremsstrahlung, Compton scattering, and axiorecombination, the "BCA processes." Based on a new calculation of this flux, including for the first time axio-recombination, we derive limits on the axion-electron Yukawa coupling gae and axion-photon interaction strength ga using the CAST phase-I data (vacuum phase). For ma <~ 10 meV/c2 we find ga gae < 8.1 × 10−23 GeV−1 at 95% CL. We stress that a next-generation axion helioscope such as the proposed IAXO could push this sensitivity into a range beyond stellar energy-loss limits and test the hypothesis that white-dwarf cooling is dominated by axion emission.
Forest fragmentation and selective logging are two main drivers of global environmental change and modify biodiversity and environmental conditions in many tropical forests. The consequences of these changes for the functioning of tropical forest ecosystems have rarely been explored in a comprehensive approach. In a Kenyan rainforest, we studied six animal-mediated ecosystem processes and recorded species richness and community composition of all animal taxa involved in these processes. We used linear models and a formal meta-analysis to test whether forest fragmentation and selective logging affected ecosystem processes and biodiversity and used structural equation models to disentangle direct from biodiversity-related indirect effects of human disturbance on multiple ecosystem processes. Fragmentation increased decomposition and reduced antbird predation, while selective logging consistently increased pollination, seed dispersal and army-ant raiding. Fragmentation modified species richness or community composition of five taxa, whereas selective logging did not affect any component of biodiversity. Changes in the abundance of functionally important species were related to lower predation by antbirds and higher decomposition rates in small forest fragments. The positive effects of selective logging on bee pollination, bird seed dispersal and army-ant raiding were direct, i.e. not related to changes in biodiversity, and were probably due to behavioural changes of these highly mobile animal taxa. We conclude that animal-mediated ecosystem processes respond in distinct ways to different types of human disturbance in Kakamega Forest. Our findings suggest that forest fragmentation affects ecosystem processes indirectly by changes in biodiversity, whereas selective logging influences processes directly by modifying local environmental conditions and resource distributions. The positive to neutral effects of selective logging on ecosystem processes show that the functionality of tropical forests can be maintained in moderately disturbed forest fragments. Conservation concepts for tropical forests should thus include not only remaining pristine forests but also functionally viable forest remnants.
Active chlorine species play a dominant role in the catalytic destruction of stratospheric ozone in the polar vortices during the late winter and early spring seasons. Recently, the correct understanding of the ClO dimer cycle was challenged by the release of new laboratory absorption cross sections (Pope et al., 2007) yielding significant model underestimates of observed ClO and ozone loss (von Hobe et al., 2007). Under this aspect, nocturnal Arctic stratospheric limb emission measurements carried out by the balloon version of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS-B) from Kiruna (Sweden) on 11 January 2001 and 20/21 March 2003 have been reanalyzed with regard to the chlorine reservoir species ClONO2 and the active species, ClO and ClOOCl (Cl2O2). New laboratory measurements of IR absorption cross sections of ClOOCl for various temperatures and pressures allowed for the first time the retrieval of ClOOCl mixing ratios from remote sensing measurements. High values of active chlorine (ClOx) of roughly 2.3 ppbv at 20 km were observed by MIPAS-B in the cold mid-winter Arctic vortex on 11 January 2001. While nighttime ClOOCl shows enhanced values of nearly 1.1 ppbv at 20 km, ClONO2 mixing ratios are less than 0.1 ppbv at this altitude. In contrast, high ClONO2 mixing ratios of nearly 2.4 ppbv at 20 km have been observed in the late winter Arctic vortex on 20 March 2003. No significant ClOx amounts are detectable on this date since most of the active chlorine has already recovered to its main reservoir species ClONO2. The observed values of ClOx and ClONO2 are in line with the established polar chlorine chemistry. The thermal equilibrium constants between the dimer formation and its dissociation, as derived from the balloon measurements, are on the lower side of reported data and in good agreement with values recommended by von Hobe et al. (2007). Calculations with the ECHAM/MESSy Atmospheric Chemistry model (EMAC) using established kinetics show similar chlorine activation and deactivation, compared to the measurements in January 2001 and March 2003, respectively.
Active chlorine species play a dominant role in the catalytic destruction of stratospheric ozone in the polar vortices during the late winter and early spring seasons. Recently, the correct understanding of the ClO dimer cycle was challenged by the release of new laboratory absorption cross sections (Pope et al., 2007) yielding significant model underestimates of observed ClO and ozone loss (von Hobe et al., 2007). Under this aspect, Arctic stratospheric limb emission measurements carried out by the balloon version of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS-B) from Kiruna (Sweden) on 11 January 2001 and 20/21 March 2003 have been reanalyzed with regard to the chlorine reservoir species ClONO2 and the active species, ClO and ClOOCl (Cl2O2). New laboratory measurements of IR absorption cross sections of ClOOCl for various temperatures and pressures allowed for the first time the retrieval of ClOOCl mixing ratios from remote sensing measurements. High values of active chlorine (ClOx) of roughly 2.3 ppbv at 20 km were observed by MIPAS-B in the cold mid-winter Arctic vortex on 11 January 2001. While nighttime ClOOCl shows enhanced values of nearly 1.1 ppbv at 20 km, ClONO2 mixing ratios are less than 0.1 ppbv at this altitude. In contrast, high ClONO2 mixing ratios of nearly 2.4 ppbv at 20 km have been observed in the late winter Arctic vortex on 20 March 2003. No significant ClOx amounts are detectable on this date since most of the active chlorine has already recovered to its main reservoir species ClONO2. The observed values of ClOx and ClONO2 are in line with the established chlorine chemistry. The thermal equilibrium constants between the dimer formation and its dissociation, as derived from the balloon measurements, are on the lower side of reported data and in good agreement with values recommended by von Hobe et al. (2007). Calculations with the ECHAM/MESSy Atmospheric Chemistry model (EMAC) using established kinetics show similar chlorine activation and deactivation, compared to the measurements in January 2001 and March 2003, respectively.
We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine non-statistical fluctuations, perhaps related to a first or second order QCD phase transition. Such fluctuations are shown to be very small.