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Aging is accompanied by the accumulation of oxidized proteins. To remove them, cells employ the proteasomal and autophagy-lysosomal systems; however, if the clearance rate is inferior to its formation, protein aggregates form as a hallmark of proteostasis loss. In cells, during stress conditions, actin aggregates accumulate leading to impaired proliferation and reduced proteasomal activity, as observed in cellular senescence. The heat shock protein 90 (Hsp90) is a molecular chaperone that binds and protects the proteasome from oxidative inactivation. We hypothesized that in oxidative stress conditions a malfunction of Hsp90 occurs resulting in the aforementioned protein aggregates. Here, we demonstrate that upon oxidative stress Hsp90 loses its function in a highly specific non-enzymatic iron-catalyzed oxidation event and its breakdown product, a cleaved form of Hsp90 (Hsp90cl), acquires a new function in mediating the accumulation of actin aggregates. Moreover, the prevention of Hsp90 cleavage reduces oxidized actin accumulation, whereas transfection of the cleaved form of Hsp90 leads to an enhanced accumulation of oxidized actin. This indicates a clear role of the Hsp90cl in the aggregation of oxidized proteins.
Diet-induced hyperglycemia is described as one major contributor to the formation of advanced glycation end products (AGEs) under inflammatory conditions, crucial in type 2 diabetes progression. Previous studies have indicated high postprandial plasma AGE-levels in diabetic patients and after long-term carbohydrate feeding in animal models. Pancreatic islets play a key role in glucose metabolism; thus, their susceptibility to glycation reactions due to high amounts of dietary carbohydrates is of special interest. Therefore, diabetes-prone New Zealand Obese (NZO) mice received either a carbohydrate-free, high-fat diet (CFD) for 11 weeks or were additionally fed with a carbohydrate-rich diet (CRD) for 7 days. In the CRD group, hyperglycemia and hyperinsulinemia were induced accompanied by increasing plasma 3-nitrotyrosine (3-NT) levels, higher amounts of 3-NT and inducible nitric oxide synthase (iNOS) within pancreatic islets. Furthermore, N-epsilon-carboxymethyllysine (CML) was increased in the plasma of CRD-fed NZO mice and substantially higher amounts of arg-pyrimidine, pentosidine and the receptor for advanced glycation end products (RAGE) were observed in pancreatic islets. These findings indicate that a short-term intervention with carbohydrates is sufficient to form endogenous AGEs in plasma and pancreatic islets of NZO mice under hyperglycemic and inflammatory conditions.
Study region: Tisza and Prut catchments, originating on the slopes of the Carpathian mountains. Study focus: The study reported here investigates (i) climate change impacts on flood risk in the region, and (ii) uncertainty related to hydrological modelling, downscaling techniques and climate projections. The climate projections used in the study were derived from five GCMs, downscaled either dynamically with RCMs or with the statistical downscaling model XDS. The resulting climate change scenarios were applied to drive the eco-hydrological model SWIM, which was calibrated and validated for the catchments in advance using observed climate and hydrological data. The changes in the 30-year flood hazards and 98 and 95 percentiles of discharge were evaluated for the far future period (2071-2100) in comparison with the reference period (1981-2010). New hydrological insights for the region: The majority of model outputs under RCP 4.5 show a small to strong increase of the 30-year flood level in the Tisza ranging from 4.5% to 62%, and moderate increase in the Prut ranging from 11% to 22%. The impact results under RCP 8.5 are more uncertain with changes in both directions due to high uncertainties in GCM-RCM climate projections, downscaling methods and the low density of available climate stations.
Background: There is a growing interest in the role of inflammageing for chronic disease development. Cytokines are potent soluble immune mediators that can be used as target biomarkers of inflammageing; however, their measurement in human samples has been challenging. This study aimed to assess the reliability of a pro- and anti-inflammatory cytokine panel in a sample of healthy people measured with a novel electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD), and to characterize their associations with metabolic and inflammatory phenotypes.
Immunological responses of hibernating mammals are suppressed at low body temperatures, a possible explanation for the devastating effect of the white-nose syndrome on hibernating North American bats. However, European bats seem to cope well with the fungal causative agent of the disease. To better understand the immune response of hibernating bats, especially against fungal pathogens, we challenged European greater mouse-eared bats (Myotis myotis) by inoculating the fungal antigen zymosan. We monitored torpor patterns, immune gene expressions, different aspects of the acute phase response and plasma oxidative status markers, and compared them with sham-injected control animals at 30 min, 48 h and 96 h after inoculation. Torpor patterns, body temperatures, body masses, white blood cell counts, expression of immune genes, reactive oxygen metabolites and non-enzymatic antioxidant capacity did not differ between groups during the experiment. However, zymosan injected bats had significantly higher levels of haptoglobin than the control animals. Our results indicate that hibernating greater mouse-eared bats mount an inflammatory response to a fungal challenge, with only mild to negligible consequences for the energy budget of hibernation. Our study gives a first hint that hibernating European bats may have evolved a hibernation-adjusted immune response in order to balance the trade-off between competent pathogen elimination and a prudent energy-saving regime.
For centuries, Amaranthus sp. were used as food, ornamentals, and medication. Molecular mechanisms, explaining the health beneficial properties of amaranth, are not yet understood, but have been attributed to secondary metabolites, such as phenolic compounds. One of the most abundant phenolic compounds in amaranth leaves is 2-caffeoylisocitric acid (C-IA) and regarding food occurrence, C-IA is exclusively found in various amaranth species. In the present study, the anti-inflammatory activity of C-IA, chlorogenic acid, and caffeic acid in LPS-challenged macrophages (RAW 264.7) has been investigated and cellular contents of the caffeic acid derivatives (CADs) were quantified in the cells and media. The CADs were quantified in the cell lysates in nanomolar concentrations, indicating a cellular uptake. Treatment of LPS-challenged RAW 264.7 cells with 10 µM of CADs counteracted the LPS effects and led to significantly lower mRNA and protein levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin 6, by directly decreasing the translocation of the nuclear factor κB/Rel-like containing protein 65 into the nucleus. This work provides new insights into the molecular mechanisms that attribute to amaranth’s anti-inflammatory properties and highlights C-IA’s potential as a health-beneficial compound for future research.
IMPORTANCE Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions. However, its potential link with CRC has not been sufficiently explored. OBJECTIVE To evaluate the prospective association of circulating plasma chemerin concentrations with incident CRC. DESIGN, SETTING, AND PARTICIPANTS Prospective case-cohort study based on 27 548 initially healthy participants from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort who were followed for up to 16 years. Baseline study information and samples were collected between August 23, 1994, and September 25, 1998. Recruitment was according to random registry sampling from the geographical area of Potsdam, Germany, and surrounding municipalities. The last date of study follow-up was May 10, 2010. Statistical analysis was conducted in 2018. MAIN OUTCOMES AND MEASURES Incident CRC, colon cancer, and rectal cancer. Baseline chemerin plasma concentrations were measured by enzyme-linked immunosorbent assay. CONCLUSIONS AND RELEVANCE This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis.
The Caucasian lynx, Lynx lynx dinniki, has one of the southernmost distributions in the Eurasian lynx range, covering Anatolian Turkey, the Caucasus and Iran. Little is known about the biology and the genetic status of this subspecies. To collect baseline genetic, ecological and behavioural data and benefit future conservation of L. l. dinniki, we monitored 11 lynx territories (396 km(2)) in northwestern Anatolia. We assessed genetic diversity of this population by non-invasively collecting 171 faecal samples and trapped and sampled 12 lynx individuals using box traps. We observed high allelic variation at 11 nuclear microsatellite markers, and found no signs of inbreeding despite the potential isolation of this population. We obtained similar numbers of distinct genotypes from the two sampling sources. Our results indicated that first order female relatives occupy neighbouring territories (female philopatry) and that territorial male lynx were highly unrelated to each other and to female territorial lynx, suggesting long distance male dispersal. Particular male and female resident territorial lynx and their offspring (kittens and subadults) were more likely to be trapped than resident floaters or dispersing (unrelated) lynx. Conversely, we obtained more data for unrelated lynx and higher numbers of territorials using non-invasive sampling (faeces). When invasive and non-invasive samples were analysed separately, the spatial organisation of lynx (in terms of female philopatry and females and males occupying permanent ranges) affected measures of genetic diversity in such a way that estimates of genetic diversity were reduced if only invasive samples were considered. It appears that, at small spatial scales, invasive sampling using box traps may underestimate the genetic diversity in carnivores with permanent ranges and philopatry such as the Eurasian lynx. As non-invasive sampling can also provide additional data on diet and spatial organisation, we advocate the use of such samples for conservation genetic studies of vulnerable, endangered or data deficient territorial species.
The particle-in-cell (PIC) method was developed to investigate microscopic phenomena, and with the advances in computing power, newly developed codes have been used for several fields, such as astrophysical, magnetospheric, and solar plasmas. PIC applications have grown extensively, with large computing powers available on supercomputers such as Pleiades and Blue Waters in the US. For astrophysical plasma research, PIC methods have been utilized for several topics, such as reconnection, pulsar dynamics, non-relativistic shocks, relativistic shocks, and relativistic jets. PIC simulations of relativistic jets have been reviewed with emphasis placed on the physics involved in the simulations. This review summarizes PIC simulations, starting with the Weibel instability in slab models of jets, and then focuses on global jet evolution in helical magnetic field geometry. In particular, we address kinetic Kelvin-Helmholtz instabilities and mushroom instabilities.
Planetary boundary layer height by means of lidar and numerical simulations over New Delhi, India
(2019)
In this work, the height of the planetary boundary layer (PBLH) is investigated over Gwal Pahari (Gual Pahari), New Delhi, for almost a year. To this end, ground-based measurements from a multiwavelength Raman lidar were used. The modified wavelet covariance transform (WCT) method was utilized for PBLH retrievals. Results were compared to data from Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) and the Weather Research and Forecasting (WRF) model. In order to examine the difficulties of PBLH detection from lidar, we analyzed three cases of PBLH diurnal evolution under different meteorological and aerosol load conditions. In the presence of multiple aerosol layers, the employed algorithm exhibited high efficiency (r = 0.9) in the attribution of PBLH, whereas weak aerosol gradients induced high variability in the PBLH. A sensitivity analysis corroborated the stability of the utilized methodology. The comparison with CALIPSO observations yielded satisfying results (r = 0.8), with CALIPSO slightly overestimating the PBLH. Due to the relatively warmer and drier winter and, correspondingly, colder and rainier pre-monsoon season, the seasonal PBLH cycle during the measurement period was slightly weaker than the cycle expected from long-term climate records.
In this paper, we investigate the continuous version of modified iterative Runge–Kutta-type methods for nonlinear inverse ill-posed problems proposed in a previous work. The convergence analysis is proved under the tangential cone condition, a modified discrepancy principle, i.e., the stopping time T is a solution of ∥𝐹(𝑥𝛿(𝑇))−𝑦𝛿∥=𝜏𝛿+ for some 𝛿+>𝛿, and an appropriate source condition. We yield the optimal rate of convergence.
Sulfate deprivation triggers high methane production in a disturbed and rewetted coastal peatland
(2019)
In natural coastal wetlands, high supplies of marine sulfate suppress methanogenesis. Coastal wetlands are, however, often subject to disturbance by diking and drainage for agricultural use and can turn to potent methane sources when rewetted for remediation. This suggests that preceding land use measures can suspend the sulfate-related methane suppressing mechanisms. Here, we unravel the hydrological relocation and biogeochemical S and C transformation processes that induced high methane emissions in a disturbed and rewetted peatland despite former brackish impact. The underlying processes were investigated along a transect of increasing distance to the coastline using a combination of concentration patterns, stable isotope partitioning, and analysis of the microbial community structure. We found that diking and freshwater rewetting caused a distinct freshening and an efficient depletion of the brackish sulfate reservoir by dissimilatory sulfate reduction (DSR). Despite some legacy effects of brackish impact expressed as high amounts of sedimentary S and elevated electrical conductivities, contemporary metabolic processes operated mainly under sulfate-limited conditions. This opened up favorable conditions for the establishment of a prospering methanogenic community in the top 30-40 cm of peat, the structure and physiology of which resemble those of terrestrial organic-rich environments. Locally, high amounts of sulfate persisted in deeper peat layers through the inhibition of DSR, probably by competitive electron acceptors of terrestrial origin, for example Fe(III). However, as sulfate occurred only in peat layers below 30-40 cm, it did not interfere with high methane emissions on an ecosystem scale. Our results indicate that the climate effect of disturbed and remediated coastal wetlands cannot simply be derived by analogy with their natural counterparts. From a greenhouse gas perspective, the re-exposure of diked wetlands to natural coastal dynamics would literally open up the floodgates for a replenishment of the marine sulfate pool and therefore constitute an efficient measure to reduce methane emissions.
Microbial community composition and abundance after millennia of submarine permafrost warming
(2019)
Warming of the Arctic led to an increase in permafrost temperatures by about 0.3 degrees C during the last decade. Permafrost warming is associated with increasing sediment water content, permeability, and diffusivity and could in the long term alter microbial community composition and abundance even before permafrost thaws. We studied the long-term effect (up to 2500 years) of submarine permafrost warming on microbial communities along an onshore-offshore transect on the Siberian Arctic Shelf displaying a natural temperature gradient of more than 10 degrees C. We analysed the in situ development of bacterial abundance and community composition through total cell counts (TCCs), quantitative PCR of bacterial gene abundance, and amplicon sequencing and correlated the microbial community data with temperature, pore water chemistry, and sediment physicochemical parameters. On timescales of centuries, permafrost warming coincided with an overall decreasing microbial abundance, whereas millennia after warming microbial abundance was similar to cold onshore permafrost. In addition, the dissolved organic carbon content of all cores was lowest in submarine permafrost after millennial-scale warming. Based on correlation analysis, TCC, unlike bacterial gene abundance, showed a significant rank-based negative correlation with increasing temperature, while bacterial gene copy numbers showed a strong negative correlation with salinity. Bacterial community composition correlated only weakly with temperature but strongly with the pore water stable isotopes delta O-18 and delta D, as well as with depth. The bacterial community showed substantial spatial variation and an overall dominance of Actinobacteria, Chloroflexi, Firmicutes, Gemmatimonadetes, and Proteobacteria, which are amongst the microbial taxa that were also found to be active in other frozen permafrost environments. We suggest that, millennia after permafrost warming by over 10 degrees C, microbial community composition and abundance show some indications for proliferation but mainly reflect the sedimentation history and paleoenvironment and not a direct effect through warming.
Core Ideas
3D MRI relaxation time maps reflect water mobility in root, rhizosphere, and soil.
3D NCT water content maps of the same plant complement relaxation time maps.
The relaxation time T1 decreases from soil to root, whereas water content increases.
Parameters together indicate modification of rhizosphere pore space by gel phase.
The zone of reduced T1 corresponds to the zone remaining dry after rewetting.
In situ investigations of the rhizosphere require high‐resolution imaging techniques, which allow a look into the optically opaque soil compartment. We present the novel combination of magnetic resonance imaging (MRI) and neutron computed tomography (NCT) to achieve synergistic information such as water mobility in terms of three‐dimensional (3D) relaxation time maps and total water content maps. Besides a stationary MRI scanner for relaxation time mapping, we used a transportable MRI system on site in the NCT facility to capture rhizosphere properties before desiccation and after subsequent rewetting. First, we addressed two questions using water‐filled test capillaries between 0.1 and 5 mm: which root diameters can still be detected by both methods, and to what extent are defined interfaces blurred by these imaging techniques? Going to real root system architecture, we demonstrated the sensitivity of the transportable MRI device by co‐registration with NCT and additional validation using X‐ray computed tomography. Under saturated conditions, we observed for the rhizosphere in situ a zone with shorter T1 relaxation time across a distance of about 1 mm that was not caused by reduced water content, as proven by successive NCT measurements. We conclude that the effective pore size in the pore network had changed, induced by a gel phase. After rewetting, NCT images showed a dry zone persisting while the MRI intensity inside the root increased considerably, indicating water uptake from the surrounding bulk soil through the still hydrophobic rhizosphere. Overall, combining NCT and MRI allows a more detailed analysis of the rhizosphere's functioning.
Deformation associated with plate convergence at subduction zones is accommodated by a complex system involving fault slip and viscoelastic flow. These processes have proven difficult to disentangle. The 2010 M-w 8.8 Maule earthquake occurred close to the Chilean coast within a dense network of continuously recording Global Positioning System stations, which provide a comprehensive history of surface strain. We use these data to assemble a detailed picture of a structurally controlled megathrust fault frictional patchwork and the three-dimensional rheological and time-dependent viscosity structure of the lower crust and upper mantle, all of which control the relative importance of afterslip and viscoelastic relaxation during postseismic deformation. These results enhance our understanding of subduction dynamics including the interplay of localized and distributed deformation during the subduction zone earthquake cycle.
The large, shallow earthquakes at Northridge, California (1994), Chi-Chi, Taiwan (1999), and Wenchuan, China (2008), each triggered thousands of landslides. We have determined the position of these landslides along hillslopes, normalizing for statistical bias. The landslide patterns have a co-seismic signature, with clustering at ridge crests and slope toes. A cross-check against rainfall-induced landslide inventories seems to confirm that crest clustering is specific to seismic triggering as observed in previous studies. In our three study areas, the seismic ground motion parameters and lithologic and topographic features used do not seem to exert a primary control on the observed patterns of landslide clustering. However, we show that at the scale of the epicentral area, crest and toe clustering occur in areas with specific geological features. Toe clustering of seismically induced landslides tends to occur along regional major faults. Crest clustering is concentrated at sites where the lithology along hillslopes is approximately uniform, or made of alternating soft and hard strata, and without strong overprint of geological structures. Although earthquake-induced landslides locate higher on hillslopes in a statistically significant way, geological features strongly modulate the landslide position along the hillslopes. As a result the observation of landslide clustering on topographic ridges cannot be used as a definite indicator of the topographic amplification of ground shaking.
In active mountain belts with steep terrain, bedrock landsliding is a major erosional agent. In the Himalayas, landsliding is driven by annual hydro-meteorological forcing due to the summer monsoon and by rarer, exceptional events, such as earthquakes. Independent methods yield erosion rate estimates that appear to increase with sampling time, suggesting that rare, high-magnitude erosion events dominate the erosional budget. Nevertheless, until now, neither the contribution of monsoon and earthquakes to landslide erosion nor the proportion of erosion due to rare, giant landslides have been quantified in the Himalayas. We address these challenges by combining and analysing earthquake- and monsoon-induced landslide inventories across different timescales. With time series of 5 m satellite images over four main valleys in central Nepal, we comprehensively mapped landslides caused by the monsoon from 2010 to 2018. We found no clear correlation between monsoon properties and landsliding and a similar mean landsliding rate for all valleys, except in 2015, where the valleys affected by the earthquake featured similar to 5-8 times more landsliding than the pre-earthquake mean rate. The longterm size-frequency distribution of monsoon-induced landsliding (MIL) was derived from these inventories and from an inventory of landslides larger than similar to 0.1 km(2) that occurred between 1972 and 2014. Using a published landslide inventory for the Gorkha 2015 earthquake, we derive the size-frequency distribution for earthquakeinduced landsliding (EQIL). These two distributions are dominated by infrequent, large and giant landslides but under-predict an estimated Holocene frequency of giant landslides (> 1 km(3)) which we derived from a literature compilation. This discrepancy can be resolved when modelling the effect of a full distribution of earthquakes of variable magnitude and when considering that a shallower earthquake may cause larger landslides. In this case, EQIL and MIL contribute about equally to a total long-term erosion of similar to 2 +/- 0.75 mm yr(-1) in agreement with most thermo-chronological data. Independently of the specific total and relative erosion rates, the heavy-tailed size-frequency distribution from MIL and EQIL and the very large maximal landslide size in the Himalayas indicate that mean landslide erosion rates increase with sampling time, as has been observed for independent erosion estimates. Further, we find that the sampling timescale required to adequately capture the frequency of the largest landslides, which is necessary for deriving long-term mean erosion rates, is often much longer than the averaging time of cosmogenic Be-10 methods. This observation presents a strong caveat when interpreting spatial or temporal variability in erosion rates from this method. Thus, in areas where a very large, rare landslide contributes heavily to long-term erosion (as the Himalayas), we recommend Be-10 sample in catchments with source areas > 10 000 km(2) to reduce the method mean bias to below similar to 20 % of the long-term erosion.
Groundwater travel time distributions (TTDs) provide a robust description of the subsurface mixing behavior and hydrological response of a subsurface system. Lagrangian particle tracking is often used to derive the groundwater TTDs. The reliability of this approach is subjected to the uncertainty of external forcings, internal hydraulic properties, and the interplay between them. Here, we evaluate the uncertainty of catchment groundwater TTDs in an agricultural catchment using a 3-D groundwater model with an overall focus on revealing the relationship between external forcing, internal hydraulic properties, and TTD predictions. Eight recharge realizations are sampled from a high-resolution dataset of land surface fluxes and states. Calibration-constrained hydraulic conductivity fields (Ks fields) are stochastically generated using the null-space Monte Carlo (NSMC) method for each recharge realization. The random walk particle tracking (RWPT) method is used to track the pathways of particles and compute travel times. Moreover, an analytical model under the random sampling (RS) assumption is fit against the numerical solutions, serving as a reference for the mixing behavior of the model domain. The StorAge Selection (SAS) function is used to interpret the results in terms of quantifying the systematic preference for discharging young/old water. The simulation results reveal the primary effect of recharge on the predicted mean travel time (MTT). The different realizations of calibration-constrained Ks fields moderately magnify or attenuate the predicted MTTs. The analytical model does not properly replicate the numerical solution, and it underestimates the mean travel time. Simulated SAS functions indicate an overall preference for young water for all realizations. The spatial pattern of recharge controls the shape and breadth of simulated TTDs and SAS functions by changing the spatial distribution of particles' pathways. In conclusion, overlooking the spatial nonuniformity and uncertainty of input (forcing) will result in biased travel time predictions. We also highlight the worth of reliable observations in reducing predictive uncertainty and the good interpretability of SAS functions in terms of understanding catchment transport processes.
The 2-D distinct element method (DEM) code (PFC2D_V5) is used here to simulate the evolution of subsidence-related karst landforms, such as single and clustered sinkholes, and associated larger-scale depressions. Subsurface material in the DEM model is removed progressively to produce an array of cavities; this simulates a network of subsurface groundwater conduits growing by chemical/mechanical erosion. The growth of the cavity array is coupled mechanically to the gravitationally loaded surroundings, such that cavities can grow also in part by material failure at their margins, which in the limit can produce individual collapse sinkholes. Two end-member growth scenarios of the cavity array and their impact on surface subsidence were examined in the models: (1) cavity growth at the same depth level and growth rate; (2) cavity growth at progressively deepening levels with varying growth rates. These growth scenarios are characterised by differing stress patterns across the cavity array and its overburden, which are in turn an important factor for the formation of sinkholes and uvalalike depressions. For growth scenario (1), a stable compression arch is established around the entire cavity array, hindering sinkhole collapse into individual cavities and favouring block-wise, relatively even subsidence across the whole cavity array. In contrast, for growth scenario (2), the stress system is more heterogeneous, such that local stress concentrations exist around individual cavities, leading to stress interactions and local wall/overburden fractures. Consequently, sinkhole collapses occur in individual cavities, which results in uneven, differential subsidence within a larger-scale depression. Depending on material properties of the cavity-hosting material and the overburden, the larger-scale depression forms either by sinkhole coalescence or by widespread subsidence linked geometrically to the entire cavity array. The results from models with growth scenario (2) are in close agreement with surface morphological and subsurface geophysical observations from an evaporite karst area on the eastern shore of the Dead Sea.