Microbial communities in arctic-alpine soils show biogeographic patterns related to elevation, but the effect of fine-scale heterogeneity and possibly related temperature and soil moisture regimes ...remains unclear. We collected soil samples from different micro-topographic positions and elevational levels in two mountain regions of the Scandes, Central Norway. Microbial community composition was characterized by 16S rRNA gene amplicon sequencing and was dependent on micro-topography and elevation. Underlying environmental drivers were identified by integration of microbial community data with a comprehensive set of site-specific long-term recorded temperature and soil moisture data. Partial least square regression analysis allowed the description of ecological response patterns and the identification of the important environmental drivers for each taxonomic group. This demonstrated for the first time that taxa responding to elevation were indeed most strongly defined by temperature, rather than by other environmental factors. Micro-topography affected taxa were primarily controlled by temperature and soil moisture. In general, 5-year datasets had higher explanatory power than 1-year datasets, indicating that the microbial community composition is dependent on long-term developments of near-ground temperature and soil moisture regimes and possesses a certain resilience, which is in agreement with an often observed delayed response in global warming studies in arctic-alpine regions.
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NUK, SBMB, SBNM, UL, UM, UPUK
Background & Aims: The treatment of patients infected with hepatitis C virus (HCV) type 1 remains a challenge necessitating innovative strategies to improve treatment outcome. The extension of ...treatment duration beyond 48 weeks is one possible strategy to address this problem. Methods: The efficacy and safety of 48 weeks (group A, N = 230) vs 72 weeks (group B, N = 225) of treatment with pegylated–interferon-alfa-2a (180 μg/wk) plus ribavirin (800 mg/day) were studied in treatment-naive patients with HCV type 1 infection. On-treatment and sustained virologic response (SVR) 24 weeks after stopping treatment was assessed by qualitative reverse-transcription polymerase chain reaction (sensitivity 50 IU/mL). Results: Overall, no significant differences could be observed in the treatment outcome between both groups. End-of-treatment and SVR rates in groups A and B were 71% vs 63% and 53% vs 54%, respectively. Patients with undetectable HCV-RNA levels already at weeks 4 and 12 had excellent SVR rates ranging from 76% to 84% regardless of treatment group, whereas patients shown to be still HCV-RNA positive at week 12 achieved significantly higher SVR rates when treated for 72 instead of 48 weeks (29% vs 17%, P = .040). A particular benefit from extended treatment duration was seen in patients with low-level viremia (<6000 IU/mL) at week 12. The frequency and intensity of adverse events was similar between the 2 groups. Conclusions: Extended treatment duration generally is not recommended in HCV type 1 infection and should be reserved only for patients with slow virologic response defined as HCV-RNA positive at week 12 but negative at week 24.
NADPH oxidases (NOX), catalyzing the reduction of molecular oxygen to form the superoxide radical anion (•O₂⁻) and hydrogen peroxide (H₂O₂), are involved in several pathological conditions, such as ...stroke, diabetes, atherosclerosis, but also in chronic neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, or multiple sclerosis. GKT136901 is a novel NOX-1/4 inhibitor with potential application in the areas of diabetic nephropathy, stroke, or neurodegeneration. In the present study, we investigated additional pharmacological activities of the compound with respect to direct free radical scavenging. GKT136901 did not interact with nitric oxide (•NO), •O₂⁻, or hydroxyl radicals (•OH), but it acted as selective scavenger of peroxynitrite (PON) already in the submicromolar concentration range. Alpha synuclein (ASYN) is a protein involved in the pathogenesis of Parkinson's disease and a known target for PON-dependent tyrosine nitration. Submicromolar concentrations of GKT136901 prevented tyrosine nitration and di-tyrosine-dependent dimer formation of ASYN by PON as indicated by Western blot and mass spectrometric analysis. GKT136901 itself was degraded when exposed to PON. In a human neuronal cell model, GKT136901 prevented both the depletion of reduced intracellular glutathione, and the degeneration of neurites when present during PON treatment of the cells. When GKT136901 was applied after PON treatment, no protective effect was observed, thus excluding an impact of GKT136901 on cellular death/survival pathways. In summary, selective scavenging of PON is an additional pharmacological property of the NOX-1/4 inhibitor GKT136901, and this may add to the efficiency of the drug in several disease models.
Background & Aims: The prospective comparison of patients with acute hepatitis C virus (HCV) who spontaneously clear the virus with those who cannot achieve viral elimination and progress to chronic ...hepatitis offers the unique opportunity to analyze natural mechanisms of viral elimination.
Methods: We studied the HCV-specific CD4
+ T-cell response in 38 patients with acute HCV and correlated the clinical course with the antiviral immune response. The individual HCV-specific T-cell response was assessed in a proliferation assay (
3H-thymidine uptake) and an enzyme-linked immunospot assay.
Results: Patients were classified according to their clinical course and pattern of CD4
+ T-cell responses in 3 categories: first, patients mounting a strong and sustained antiviral CD4
+/Th1
+ T-cell response who cleared the virus (HCV RNA–negative; n = 20); second, patients who were unable to mount an HCV-specific CD4
+ T-cell response and developed chronic disease (n = 12); and third, patients who initially displayed a strong CD4
+ T-cell response and eliminated the virus (HCV PCR–negative) but subsequently lost this specific T-cell response (n = 6). The loss of the HCV-specific CD4
+ T-cell response was promptly followed by HCV recurrence.
Conclusions: The results indicate that a virus-specific CD4
+/Th1
+ T-cell response that eliminates the virus during the acute phase of disease has to be maintained permanently to achieve long-term control of the virus. The induction and/or maintenance of virus-specific CD4
+ T cells could represent a promising therapeutic approach in HCV infection.
GASTROENTEROLOGY 1999;117:933-941
An integral part of modern day synthetic organic chemistry is the design of novel reactions that proceed with high atom economy and a minimal protection strategy and that enable multiple ...transformations in a one-pot reaction sequence.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract
There is an obvious need for a better understanding of the drivers of local spatial heterogeneity in alpine phytomass. Facing challenges in scaling relations with data available either at ...biome‐scale or at plot‐scale we wanted to disentangle the driving forces behind spatial patterns of phytomass, productivity, and energy content in alpine reindeer pastures. Our hypothesis was that we would find a set of environmental variables that explain the patterns of fodder resources, thereafter facilitating a spatial upscaling of plot‐based data to the broad‐scale range of the reindeer pastures. Based on a nested stratified random design, we used univariate and multivariate statistical analyses to relate fodder resources to environmental data along fine‐scaled micro‐topographical gradients which were embedded in broad‐scaled gradients of grazing intensities and climatic conditions throughout Norway. We found that the spatial heterogeneity of resources was not sufficiently explained by our comprehensive set of commonly available environmental variables. This reveals that micro‐spatial patterns of energetic fodder resources for reindeer in alpine landscapes are miscalculated by common approaches and that the functionalities behind these micro‐spatial patterns are not yet fully understood. Hence, our results suggest that broad‐scale models cannot account for the functionality in alpine environments, highlighting that resolution, scale, and the functional context are crucial aspects in understanding broad‐scale resource patterns of reindeer pastures.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Papua New Guinea (PNG), has experienced an increase in breast cancer incidence correlating to the westernisation of the country. Increased breast density is known to increase breast cancer risk. This ...study investigates if there are any factors unique to the women of PNG that may impact breast density and breast cancer risk.
A survey was undertaken of 1,161 women who had undergone mammographic imaging at the Pacific International Hospital (PIH). Results were correlated with the five Tabár mammographic parenchymal patterns (TP), recorded for each woman and geographical location, parity, breast size, occupation, marital and menstrual status, smoking and alcohol consumption, hormone replacement therapy (HRT), and exercise. Statistical analysis was undertaken using chi-square test, Fisher's exact test and Odds Ratio (OR).
Relationships were identified between TP and parity (p < 0.001), marital status (p < 0.001), smoking (p < 0.001), alcohol intake (p = 0.029) and HRT (p = 0.029). There was no evidence of a relationship between pattern type and geographical location (p = 0.290), breast size (p = 0.592), occupation (p = 0.724), menstruation (p = 0.866) or exercise (p = 0.290). Married women, OR = 0.4004, CI 95% (0.2873–0.5579) and those with higher parity, OR 0.5034, CI 95% (0.3693–0.6862) were half as likely to have increased breast density reducing risk.
There was no clear relationship across almost all data. Factors associated with increased breast density in PNG included parity, marital status, smoking, alcohol, and HRT use were evidenced in this snapshot of PNG women. Breast cancer risk was shown to be reduced for married women and those with increased parity.
•Breast density has a relationship with parity and marital status.•Breast density has a relationship with smoking, alcohol consumption and HRT.•Breast density has no relationship with breast size or menstrual status.•Breast density has no relationship with geography, occupation or exercise.•Increased breast density was half as likely with higher parity and marriage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
CD8+ T lymphocytes play a major role in antiviral immune defense. Their significance for acute hepatitis C is unclear. Our aim was to correlate the CD8+ T cell response with the outcome of infection. ...Eighteen patients with acute hepatitis C and 19 normal donors were studied. Hepatitis C virus (HCV)—specific CD8+ T cells were identified in the enzyme-linked immunospot assay by their interferon-γ (IFN-γ) production after specific stimulation. The highest numbers of IFN-γ—producing HCV-specific CD8+ T cells were found in patients with acute hepatitis C and a self-limited course of disease during the first 6 months after onset of disease, but these numbers dropped thereafter to undetectable levels. The differences in responsiveness between patients with self-limited disease versus patients with a chronic course were statistically significant (P < .001). Our data show that the number of IFN—γ-producing HCV-specific CD8+ T cells during the first 6 months after onset of disease is associated with eradication of the HCV infection.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Climate-driven variability of habitat selection of large herbivores has not yet been explicitly analyzed. To this end, we aimed to better understand the climate-ecological mechanisms behind ...geographic patterns of reindeer (
Rangifer tarandus tarandus
) habitat utilization. Our study area comprised of the ranges of Filefjell Reinlag, southern Norway (60°20′-61°20′ N; 8°20′-9°50′ E). We analyzed habitat selection of 20 (± 2) GPS-collared female reindeer over a period of five years. We examined the mechanistic forces of habitat selection variability by applying a novel stepwise factor analysis approach based on the niche concept. We characterized the governing conditions for inductively delineated seasons and extracted in a first step for each year the seasonal scores of the individual animals on the environmental variables to explain their habitat use. For each season, we then conducted principal component analyses (PCA) to analyze the inter-annual variability in habitat preferences using the individual scores for the environmental variables per year. In a third step, we fit our potential drivers as vectors onto each seasonal PCA and retained solely significant drivers. Our results reveal complex spatiotemporal patterns of habitat selection that are driven by seasonality, year-to-year climate variability, and the choice of individual animals. In contrast to expected similarities between conspecifics, our analyses revealed varying degrees of intra-species variability and therefore suggest that responses of individual reindeer to climate variability are inconsistent. Moreover, we found annually reoccurring patterns of habitat selection strength during different seasons that help explain coping capacities of reindeer against climate variability. In contrast with our expectations, we detected a very high inter-annual variability in habitat preferences to be related to governing climatic conditions. Here, we present new evidence for the variability of response mechanisms of reindeer's habitat selection shown throughout different seasons and years that buffer alpine pastoralism against climate variability. Our work contributes to a better understanding of alpine ecological response mechanisms as a key for projections of future responses to climate change.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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