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Coastal and riverine floods are major concerns worldwide as they can impact highly populated areas and result in significant economic losses. In a river mouth environment, interacting hydrological and oceanographical processes can enhance the severity of floods. The compound flood hazards from high sea levels and high river discharge are often estimated using copulas, among other methods. Here, we systematically investigate the influence of different data sources coming from observations and models as well as the choice of copula on extreme water level estimates. While we focus on the river mouth at the city of Halmstad (Sweden), the approach presented is easily transferable to other sites. Our results show that the choice of data sources can considerably impact the results up to 10 % and 15 % for the river time series and 3 % to 4.6 % for the sea level time series under the 5- and 30-year return periods, respectively. The choice of copula can also strongly influence the outcome of such analyses up to 13 % and 9.5 % for the 5-year and 30-year return periods. Each percentage refers to the normalized difference in return level results we can expect when choosing a certain copula or input dataset. The copulas found to statistically best fit our datasets are the Clayton, BB1, and Gaussian (once) ones. We also show that the compound occurrence of high sea levels and river runoff may lead to heightened flood risks as opposed to considering them independent processes and that, in the current study, this is dominated by the hydrological driver. Our findings contribute to framing existing studies, which typically only consider selected copulas and datasets, by demonstrating the importance of considering uncertainties.

To compare in situ and laboratory estimates of sea spray aerosol (SSA) production fluxes, we conducted two research campaigns in the vicinity of an eddy covariance (EC) flux tower on the island of Östergarnsholm in the Baltic Sea during May and August 2021. To accomplish this, we performed EC flux measurements for particles with diameters between 0.25 and 2.5 µm simultaneously with laboratory measurements using a plunging jet sea spray simulation chamber containing local seawater sampled close to the footprint of the flux tower. We observed a log-linear relationship between wind speed and EC-derived SSA emission fluxes, a power-law relationship between significant wave height and EC-derived SSA emission fluxes, and a linear relationship between wave Reynolds number and EC-derived SSA emission fluxes, all of which are consistent with earlier studies. Although we observed a weak negative relationship between particle production in the sea spray simulation chamber and seawater chlorophyll-α concentration and a weak positive relationship with the concentration of fluorescent dissolved organic matter in seawater, we did not observe any significant impact of dissolved oxygen on particle production in the chamber. To obtain an estimate of the size-resolved emission spectrum for particles with dry diameters between 0.015 and 10 µm, we combined the estimates of SSA particle production fluxes obtained using the EC measurements and the chamber measurements in three different ways: (1) using the traditional continuous whitecap method, (2) using air entrainment measurements, and (3) simply scaling the chamber data to the EC fluxes. In doing so, we observed that the magnitude of the EC-derived emission fluxes compared relatively well to the magnitude of the fluxes obtained using the chamber air entrainment method as well as the previous flux measurements of Nilsson et al. (2021) and the parameterizations of Mårtensson et al. (2003) and Salter et al. (2015). As a result of these measurements, we have derived a wind-speed-dependent and wave-state-dependent SSA parameterization for particles with dry diameters between 0.015 and 10 µm for low-salinity waters such as the Baltic Sea, thus providing a more accurate estimation of SSA production fluxes.

Extreme sea levels may cause damage and the disruption of activities in coastal areas. Thus, predicting extreme sea levels is essential for coastal management. Statistical inference of robust return level estimates critically depends on the length and quality of the observed time series. Here, we compare two different methods for extending a very short (∼ 10-year) time series of tide gauge measurements using a longer time series from a neighbouring tide gauge: linear regression and random forest machine learning. Both methods are applied to stations located in the Kattegat Basin between Denmark and Sweden. Reasonable results are obtained using both techniques, with the machine learning method providing a better reconstruction of the observed extremes. By generating a set of stochastic time series reflecting uncertainty estimates from the machine learning model and subsequently estimating the corresponding return levels using extreme value theory, the spread in the return levels is found to agree with results derived by more physically based methods.

Reducing uncertainties in the air–sea CO2 flux calculations is one of the major challenges when addressing the oceanic contribution in the global carbon balance. In traditional models, the air–sea CO2 flux is estimated using expressions of the gas transfer velocity as a function of wind speed. However, other mechanisms affecting the variability in the flux at local and regional scales are still poorly understood. The uncertainties associated with the flux estimates become particularly large in heterogeneous environments such as coastal and marginal seas. Here, we investigated the air–sea CO2 exchange at a coastal site in the central Baltic Sea using 9 years of eddy covariance measurements. Based on these observations we were able to capture the temporal variability in the air–sea CO2 flux and other parameters relevant for the gas exchange. Our results show that a wind-based model with a similar pattern to those developed for larger basins and open-sea conditions can, on average, be a good approximation for k, the gas transfer velocity. However, in order to reduce the uncertainty associated with these averages and produce reliable short-term k estimates, additional physical processes must be considered. Using a normalized gas transfer velocity, we identified conditions associated with enhanced exchange (large k values). During high and intermediate wind speeds (above 6–8 m s−1), conditions on both sides of the air–water interface were found to be relevant for the gas exchange. Our findings further suggest that at such relatively high wind speeds, sea spray is an efficient mechanisms for air–sea CO2 exchange. During low wind speeds ( m s−1), water-side convection was found to be a relevant control mechanism. The effect of both sea spray and water-side convection on the gas exchange showed a clear seasonality with positive fluxes (winter conditions) being the most affected.

Non-idealized wind profiles frequently occur over the Baltic Sea and are important to take into consideration for offshore wind power, as they affect not only the power production but also the loads on the structure and the behavior of the wake behind the turbine. In this observational study, we classified non-idealized profiles as the following wind profiles having negative shear in at least one part of the lidar wind profile between 28 and 300 m: low-level jets (with a local wind maximum in the profile), profiles with a local minimum and negative profiles. Using observations spanning over 3 years, we show that these non-idealized profiles are common over the Baltic Sea in late spring and summer, with a peak of 40 % relative occurrence in May. Negative profiles (in the 28–300 m layer) mostly occurred during unstable conditions, in contrast to low-level jets that primarily occurred in stable stratification. There were indications that the strong shear zone of low-level jets could cause a relative suppression of the variance for large turbulent eddies compared to the peak of the velocity spectra, in the layer below the jet core. Swell conditions were found to be favorable for the occurrence of negative profiles and profiles with a local minimum, as the waves fed energy into the surface layer, resulting in an increase in the wind speed from below.

A natural hazard is a naturally occurring extreme event that has a negative effect on people and society or the environment. Natural hazards may have severe implications for human life and can potentially generate economic losses and damage ecosystems. A better understanding of their major causes, probability of occurrence, and consequences enables society to be better prepared to save human lives as well as to invest in adaptation options. Natural hazards related to climate change are identified as one of the Grand Challenges in the Baltic Sea region. Here, we summarize existing knowledge about extreme events in the Baltic Sea region with a focus on the past 200 years as well as on future climate scenarios. The events considered here are the major hydro-meteorological events in the region and include wind storms, extreme waves, high and low sea levels, ice ridging, heavy precipitation, sea-effect snowfall, river floods, heat waves, ice seasons, and drought. We also address some ecological extremes and the implications of extreme events for society (phytoplankton blooms, forest fires, coastal flooding, offshore infrastructure, and shipping). Significant knowledge gaps are identified, including the response of large-scale atmospheric circulation to climate change and also concerning specific events, for example, the occurrence of marine heat waves and small-scale variability in precipitation. Suggestions for future research include the further development of high-resolution Earth system models and the potential use of methodologies for data analysis (statistical methods and machine learning). With respect to the expected impacts of climate change, changes are expected for sea level, extreme precipitation, heat waves and phytoplankton blooms (increase), and cold spells and severe ice winters (decrease). For some extremes (drying, river flooding, and extreme waves), the change depends on the area and time period studied.

A night-time turbulence regime classification, the so-called “HOckey-Stick Transition ” (HOST) theory, proposed by Sun et al. (2012) from the Cooperative Atmosphere–Surface Exchange Study-1999 (CASES-99) is explored using data from the Boundary-Layer Late Afternoon and Sunset Turbulence (BLLAST) field campaign which took place during summer 2011 in the central French Pyrenean foothills. Results show that the HOST turbulence relationships for the BLLAST field campaign data are strongly dependent on both the meteorological and orographic features. The HOST pattern only appears for nights when a stably stratified boundary layer can be developed, corresponding to fair-weather and clear-sky nights, when the flow is generated by the nearby orography, from the south and the south-east. Those flows strongly influenced by the orography may generate intermittent or enhanced turbulence. When considering the whole nocturnal dataset for these flow directions, several enhanced turbulence points are found to be associated with sudden wind speed and directional shear transitions. In contrast, flows from other directions do not reproduce the HOST relationships and the turbulence relationship is almost linear, independent of vertical temperature gradients, corresponding to flows driven by synoptic scales. In addition we identify examples of gravity waves and top-down turbulent events that lead to transitions between the turbulence regimes.

The decay of turbulence kinetic energy (TKE) and its budget in the afternoon period from midday until zero-buoyancy flux at the surface is studied in a two-part paper by means of measurements from the Boundary Layer Late Afternoon and Sunset Turbulence (BLLAST) field campaign for 10 intensive observation period days. Here, in Part 1, near-surface measurements from a small tower are used to estimate a TKE budget. The overall boundary layer characteristics and mesoscale situation at the site are also described based upon taller tower measurements, radiosoundings and remote sensing instrumentation. Analysis of the TKE budget during the afternoon transition reveals a variety of different surface layer dynamics in terms of TKE and TKE decay. This is largely attributed to variations in the 8 m wind speed, which is responsible for different amounts of near-surface shear production on different afternoons and variations within some of the afternoon periods. The partitioning of near-surface production into local dissipation and transport in neutral and unstably stratified conditions was investigated. Although variations exist both between and within afternoons, as a rule of thumb, our results suggest that about 50 % of the near-surface production of TKE is compensated for by local dissipation near the surface, leaving about 50 % available for transport. This result indicates that it is important to also consider TKE transport as a factor influencing the near-surface TKE decay rate, which in many earlier studies has mainly been linked with the production terms of TKE by buoyancy and wind shear. We also conclude that the TKE tendency is smaller than the other budget terms, indicating a quasi-stationary evolution of TKE in the afternoon transition. Even though the TKE tendency was observed to be small, a strong correlation to mean buoyancy production of −0.69 was found for the afternoon period. For comparison with previous results, the TKE budget terms are normalized with friction velocity and measurement height and discussed in the framework of Monin–Obukhov similarity theory. Empirically fitted expressions are presented. Alternatively, we also suggest a non-local parametrization of dissipation using a TKE–length scale model which takes into account the boundary layer depth in addition to distance above the ground. The non-local formulation is shown to give a better description of dissipation compared to a local parametrization.

A simple model for turbulence kinetic energy (TKE) and the TKE budget is presented for sheared convective atmospheric conditions based on observations from the Boundary Layer Late Afternoon and Sunset Turbulence (BLLAST) field campaign. It is based on an idealized mixed-layer approximation and a simplified near-surface TKE budget. In this model, the TKE is dependent on four budget terms (turbulent dissipation rate, buoyancy production, shear production and vertical transport of TKE) and only requires measurements of three available inputs (near-surface buoyancy flux, boundary layer depth and wind speed at one height in the surface layer) to predict vertical profiles of TKE and TKE budget terms.This simple model is shown to reproduce some of the observed variations between the different studied days in terms of near-surface TKE and its decay during the afternoon transition reasonably well. It is subsequently used to systematically study the effects of buoyancy and shear on TKE evolution using idealized constant and time-varying winds during the afternoon transition. From this, we conclude that many different TKE decay rates are possible under time-varying winds and that generalizing the decay with simple scaling laws for near-surface TKE of the form tα may be questionable.The model's errors result from the exclusion of processes such as elevated shear production and horizontal advection. The model also produces an overly rapid decay of shear production with height. However, the most influential budget terms governing near-surface TKE in the observed sheared convective boundary layers are included, while only second-order factors are neglected. Comparison between modeled and averaged observed estimates of dissipation rate illustrates that the overall behavior of the model is often quite reasonable. Therefore, we use the model to discuss the low-turbulence conditions that form first in the upper parts of the boundary layer during the afternoon transition and are only apparent later near the surface. This occurs as a consequence of the continuous decrease in near-surface buoyancy flux during the afternoon transition. This region of weak afternoon turbulence is hypothesized to be a “pre-residual layer”, which is important in determining the onset conditions for the weak sporadic turbulence that occur in the residual layer once near-surface stratification has become stable.

This study evaluates the ability of three operational models, with resolution varying from 2.5 to 16 km, to predict the boundary-layer turbulent processes and mesoscale variability observed during the Boundary Layer Late-Afternoon and Sunset Turbulence (BLLAST) field campaign. We analyse the representation of the vertical profiles of temperature and humidity and the time evolution of near-surface atmospheric variables and the radiative and turbulent fluxes over a total of 12 intensive observing periods (IOPs), each lasting 24 h. Special attention is paid to the evolution of the turbulent kinetic energy (TKE), which was sampled by a combination of independent instruments. For the first time, this variable, a central one in the turbulence scheme used in AROME and ARPEGE, is evaluated with observations.In general, the 24 h forecasts succeed in reproducing the variability from one day to another in terms of cloud cover, temperature and boundary-layer depth. However, they exhibit some systematic biases, in particular a cold bias within the daytime boundary layer for all models. An overestimation of the sensible heat flux is noted for two points in ARPEGE and is found to be partly related to an inaccurate simplification of surface characteristics. AROME shows a moist bias within the daytime boundary layer, which is consistent with overestimated latent heat fluxes. ECMWF presents a dry bias at 2 m above the surface and also overestimates the sensible heat flux. The high-resolution model AROME resolves the vertical structures better, in particular the strong daytime inversion and the thin evening stable boundary layer. This model is also able to capture some specific observed features, such as the orographically driven subsidence and a well-defined maximum that arises during the evening of the water vapour mixing ratio in the upper part of the residual layer due to fine-scale advection. The model reproduces the order of magnitude of spatial variability observed at mesoscale (a few tens of kilometres). AROME provides a good simulation of the diurnal variability of the turbulent kinetic energy, while ARPEGE shows the right order of magnitude.

We investigate the decay of planetary boundary layer (PBL) turbulence in the afternoon, from the time the surface buoyancy flux starts to decrease until sunset. Dense observations of mean and turbulent parameters were acquired during the Boundary Layer Late Afternoon and Sunset Turbulence (BLLAST) field experiment by several meteorological surface stations, sounding balloons, radars, lidars and two aircraft during the afternoon transition. We analysed a case study based on some of these observations and large-eddy simulation (LES) data focusing on the turbulent vertical structure throughout the afternoon transition. The decay of turbulence is quantified through the temporal and vertical evolution of (1) the turbulence kinetic energy (TKE), (2) the characteristic length scales of turbulence and (3) the shape of the turbulence spectra. A spectral analysis of LES data, airborne and surface measurements is performed in order to characterize the variation in the turbulent decay with height and study the distribution of turbulence over eddy size. This study highlights the LES ability to reproduce the turbulence evolution throughout the afternoon. LESs and observations agree that the afternoon transition can be divided in two phases: (1) a first phase during which the TKE decays at a low rate, with no significant change in turbulence characteristics, and (2) a second phase characterized by a larger TKE decay rate and a change in spectral shape, implying an evolution of eddy size distribution and energy cascade from low to high wave number. The changes observed either in TKE decay (during the first phase) or in the vertical wind spectra shape (during the second phase of the afternoon transition) occur first in the upper region of the PBL. The higher within the PBL, the stronger the spectra shape changes.

A global heat flux model based on a fractional derivative of plasma pressure is proposed for the heat transport in fusion plasmas. The degree of the fractional derivative of the heat flux, α, is defined through the power balance analysis of the steady state. The model was used to obtain the experimental values of α for a large database of the Joint European Torus (JET) carbon-wall as well as ITER like-wall plasmas. The fractional degrees of the electron heat flux are found to be α

A new hygroscopic tandem differential mobility analyzer (H-TDMA) has been constructed at Lund University within the frameworks of the EU FP6 Infrastructure Project EUSAAR (http://www.eusaar.org/). The aim of this coordinated H-TDMA development is to design and evaluate a new generation of H-TDMAs that are capable of conducting long term measurements of the hygroscopic growth and state of mixing of sub-micrometer atmospheric aerosol particles at the EUSAAR aerosol super-sites across Europe. The H-TDMA constructed for this project has been validated with respect to hygroscopic growth factor, stability of relative humidity (RH), temperature stability and its ability to operate unattended for longer periods of time. When measuring growth factors of ammonium sulphate, the new H-TDMA system was found to measure within a growth factor deviation of ±0.05 compared to previously recorded data by Tang et al. (1994). The long term RH of the system has been found stable at 90.0% with a standard deviation of ±0.23% and an average temperature variability of the second DMA less than ±0.1 K. Daily automated ammonium sulphate measurements have validated the ambient measurements. The instrument is operated at the EMEP/EUSAAR background station Vavihill in the southern part of Sweden.

The hygroscopic growth and activation of two HULIS (HUmic LIke Substance) and one Aerosol-Water-Extract sample, prepared from urban-type aerosol, were investigated. All samples were extracted from filters, redissolved in water and atomized for the investigations presented here. The hygroscopic growth measurements were done using LACIS (Leipzig Aerosol Cloud Interaction Simulator) together with a HH-TDMA (High Humidity Tandem Differential Mobility Analyzer). Hygroscopic growth was determined for relative humidities (RHs) up to 99.75%. The critical diameters for activation were measured for supersaturations between 0.2 and 1%. All three samples showed a similar hygroscopic growth behavior, and the two HULIS samples also were similar in their activation behavior, while the Aerosol-Water-Extract turned out to be more CCN active than the HULIS samples. The experimental data was used to derive parameterizations for the hygroscopic growth and activation of HULIS particles. The concept of ρion (Wex et al., 2007a) and the Szyszkowski-equation (Szyszkowski, 1908; Facchini, 1999) were used for parameterizing the Raoult and the Kelvin (surface tension) terms of the Köhler equation, respectively. This concept proved to be very successful for the HULIS samples in the saturation range from RHs larger than 98% up to activation. It was also shown to work well with data on HULIS taken from literature. Here, different atmospheric life-times and/or different sources for the different samples showed up in different coefficients for the parameterization. However, the parameterization did not work out well for the Aerosol-Water-Extract.

Signal crayfish (Pacifastacus leniusculus) have become increasingly widespread in rivers in Great Britain since their introduction in the late 1970s, causing extensive losses of indigenous white-clawed crayfish and negative impacts on communities of aquatic plants, invertebrates and benthic fish. Angling interests are increasingly concerned about possible impacts of signal crayfish on brown trout, sea trout (Salmo trutta) and Atlantic salmon (S. salar). This study of a limestone headwater stream in the Pennine uplands, Yorkshire, compares density of fish and two species of crayfish in two years. Signal crayfish are progressively replacing white-clawed crayfish. Surveys showed a significant negative relationship between the fish and signal crayfish. Sites with white-clawed crayfish (1–2 crayfish/trap night) had abundant juvenile trout (> 47·100 m−2). Signal crayfish reached higher abundance (4–8 crayfish/trap night) and those sites had fewer fish (0 − 18.8·100 m−2). The signal crayfish population will expand to other tributaries over time. If similar reduction of salmonid recruitment occurs in those streams, there is potential for significant impacts on an important recreational fishery.

H2DCF-DA (dihydrodichlorofluorescein diacetate) is widely used to evaluate ‘cellular oxidative stress’. After passing through the plasma membrane, this lipophilic and non-fluorescent compound is de-esterified to a hydrophilic alcohol [H2DCF (dihydrodichlorofluorescein)] that may be oxidized to fluorescent DCF (2′,7′-dichlorofluorescein) by a process usually considered to involve ROS (reactive oxygen species). It is, however, not always recognized that, being a hydrophilic molecule, H2DCF does not cross membranes, except for the outer fenestrated mitochondrial ones. It is also not generally realized that oxidation of H2DCF is dependent either on Fenton-type reactions or on unspecific enzymatic oxidation by cytochrome c, for neither superoxide, nor H2O2, directly oxidizes H2DCF. Consequently, oxidation of H2DCF requires the presence of either cytochrome c or of both redox-active transition metals and H2O2. Redox-active metals exist mainly within lysosomes, whereas cytochrome c resides bound to the outer side of the inner mitochondrial membrane. Following exposure to H2DCF-DA, weak mitochondrial fluorescence was found in both the oxidation-resistant ARPE-19 cells and the much more sensitive J774 cells. This fluorescence was only marginally enhanced following short exposure to H2O2, showing that by itself it is unable to oxidize H2DCF. Cells that were either exposed to the lysosomotropic detergent MSDH (O-methylserine dodecylamide hydrochloride), exposed to prolonged oxidative stress, or spontaneously apoptotic showed lysosomal permeabilization and strong DCF-induced fluorescence. The results suggest that DCF-dependent fluorescence largely reflects relocation to the cytosol of lysosomal iron and/or mitochondrial cytochrome c. [ABSTRACT FROM AUTHOR]

The fastest swimming fishes in relation to size are found among coral reef fish larvae on their way to settle on reefs. By testing two damselfishes, Chromis atripectoralis and Pomacentrus amboinensis, we show that the high swimming speeds of the pre-settlement larvae are accompanied by the highest rates of oxygen uptake ever recorded in ectothermic vertebrates. As expected, these high rates of oxygen uptake occur at the cost of poor hypoxia tolerance. However, hypoxia tolerance is needed when coral reef fishes seek nocturnal shelter from predators within coral colonies, which can become severely hypoxic microhabitats at night. When the larvae settle on the reef, we found that they go through a striking respiratory transformation, i.e. the capacity for rapid oxygen uptake falls, while the ability for high-affinity oxygen uptake at low oxygen levels is increased. This transition to hypoxia tolerance is needed when they settle on the reef; this was strengthened by our finding that small resident larvae of Acanthochromis polyacanthus, a damselfish lacking a planktonic larval stage, do not display such a transition, being well adapted to hypoxia and showing relatively low maximum rates of oxygen uptake that change little with age. [ABSTRACT FROM AUTHOR]

Objectives: To apply the normalized resistance interpretation (NRI) method to Etest MIC results which have higher precision than conventional log2 dilution MIC tests due to the inclusion of intermediate values. If successful, NRI might provide an objective tool for the definition of epidemiological MIC cut-off values.Methods: MICs of tigecycline and other antimicrobial agents were determined for 4771 clinical isolates comprising five Gram-positive and 13 Gram-negative species or species groups using the Etest. Histograms of MIC values were constructed for each species and NRI calculations were applied to them. An upper MIC limit of 2.5 SD above the theoretical mean of the normalized distribution was used for setting the epidemiological cut-off values.Results: Calculated cut-off values for wild-type strains were between 0.11 and 0.96 mg/L for Gram-positive species, and between 0.44 and 8.3 mg/L for Gram-negative species, except for Pseudomonas aeruginosa, which had a cut-off value of 450 mg/L, consistent with earlier reports on the lack of activity of tigecycline against this species.Conclusions: NRI offers an objective method for the analysis of MICs produced using Etests and the determination of epidemiological MIC cut-off values. [ABSTRACT FROM AUTHOR]

Mouthbrooding occurs among several groups of fishes. Although a mouth full of eggs can be expected to pose a considerable respiratory problem, to our knowledge no study has examined respiratory consequences of mouthbrooding in fishes, or how hypoxia or strenuous swimming may affect the success of this reproductive strategy. In two species of cardinalfish (Apogon fragilis and Apogon leptacanthus), from the reef at Lizard Island (Great Barrier Reef), we found that mouthbrooding significantly reduced the ability to take up oxygen at low ambient oxygen levels. While the direct energetic cost of mouthbrooding appeared insignificant at rest in well-oxygenated water, mouthbrooding significantly reduced the respiratory scope of the fishes and their capacity for sustained aerobic swimming. The males spat out their eggs in hypoxia. Interestingly, the species with the larger brood, A. fragilis, spat out the brood at a higher water [O2] than did A. leptacanthus, which had a smaller mean brood mass. Moreover, in contrast to mouthbrooding A. leptacanthus, mouthbrooding A. fragilis was unable to increase its ventilatory frequency in response to hypoxia. This suggests a trade-off situation between hypoxia tolerance and brood size. Apparently, A. fragilis has sacrificed hypoxia tolerance in favour of a large brood size to a greater extent than has A. leptacanthus. [ABSTRACT FROM AUTHOR]

SUMMARY:: While medical science has struggled to find ways to counteract anoxic brain damage with limited success, evolution has repeatedly solved this problem. The best-studied examples of anoxia-tolerant vertebrates are the crucian carp and some North American Freshwater turtles. These can survive anoxia for days to months, depending of temperature. Both animals successfully fight any major fall in brain ATP levels, but the strategies they use to accomplish this are quite divergent. The anoxic turtle suppresses brain activity to such a degree that it becomes virtually comatose. The underlying mechanisms involve closing down ion conductances and releasing GABA and adenosine. By contrast, the crucian carp remains active in anoxia, although it suppresses selected brain functions, and avoids lactate self-poisoning by producing an exotic anaerobic end-product. These animals provide unique models for studying anoxic survival mechanisms both on a molecular and physiological level. [ABSTRACT FROM AUTHOR]

While the family-based analysis of genetic and environmental contributions to continuous or Gaussian traits is now straightforward using the linear mixed models approach, the corresponding analysis of complex binary traits is still rather limited. In the latter we usually rely on twin studies or pairs of relatives, but these studies often have limited sample size or have difficulties in dealing with the dependence between the pairs. Direct analysis of extended family data can potentially overcome these limitations. In this paper, we will describe various genetic models that can be analysed using an extended family structure. We use the generalized linear mixed model to deal with the family structure and likelihood-based methodology for parameter inference. The method is completely general, accommodating arbitrary family structures and incomplete data. We illustrate the methodology in great detail using the Swedish birth registry data on pre-eclampsia, a hypertensive condition induced by pregnancy. The statistical challenges include the specification of sensible models that contain a relatively large number of variance components compared to standard mixed models. In our illustration the models will account for maternal or foetal genetic effects, environmental effects, or a combination of these and we show how these effects can be readily estimated using family data. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Using respirometry, we examined the hypoxia tolerance of 31 teleost fish species (seven families) inhabiting coral reefs at a 2–5 m depth in the lagoon at Lizard Island (Great Barrier Reef, Australia). All fishes studied maintained their rate of oxygen consumption down to relatively severe hypoxia (20–30% air saturation). Indeed, most fishes appeared unaffected by hypoxia until the oxygen level fell below 10% of air saturation. This, hitherto unrecognized, hypoxia tolerance among coral reef fishes could reflect adaptations to nocturnal hypoxia in tide pools. It may also be needed to enable fishes to reside deep within branching coral at night to avoid predation. Widespread hypoxia tolerance in a habitat with such an extreme biodiversity as coral reefs indicate that there is a wealth of hypoxia related adaptations to be discovered in reef fishes. [ABSTRACT FROM AUTHOR]

Abstract Deep learning involves an artificial intelligence (AI) approach and has been shown to provide superior performance for automating image recognition tasks, as well as exceeding human capabilities in both time and accuracy. Histopathology diagnostics is one of the more popular challenges at the intersection of artificial intelligence, computer vision, and medicine. Developing methods to automatically detect and identify pathologies in digitized histology slides imposes unique challenges due to the large size of these images and the complexity of the features present in biological tissue. Most methods that are capable of human-level recognition in histopathology are tuned to a specific problem since the computational complexity exceeds that of traditional image classification problems. In the current study, a deep learning approach is developed and presented that can be trained to locate and accurately classify different types of pathologies in gigapixel digitized histology slides along with completing the binary disease classification for the entire image. The approach uses a novel pyramid tiling approach to take advantage of spatial awareness around the area to be classified, while maintaining efficiency and scalability for gigapixel images. The approach is trained and validated on a wide variety of tissue types (i.e., testis, ovary, prostate, kidney) and pathologies taken from an epigenetically altered histology study at Washington State University. The newly developed procedure was optimized and validated along with comparison and validation on public histology datasets. The current developed procedure was found to be optimal and more reproducible when compared to manual procedures, and optimal to previous protocols that used fragmented tissue or slide analysis. Observations demonstrate that the deep learning histopathology analysis is significantly more efficient and accurate than standard manual histopathology analysis.

ABSTRACT Local delivery of antibiotics as prophylaxis for prosthetic joint infections (PJIs) is frequently used during total hip replacement surgery. Morselized bone allograft impregnated with vancomycin and tobramycin (TobraVanc) could provide effective prophylaxis against bacteria commonly associated with PJIs. In this study, the concentrations of antibiotics released by bone allograft impregnated with TobraVanc were determined by using an in vitro bioassay system entailing measuring inhibition zone diameters caused by antibiotic-impregnated bone chips cast in agar against standard curves. The concentrations were determined in samples of TobraVanc-impregnated bone graft taken before and after the application of the bone graft in the patients undergoing acetabular revision surgery. Antibiotic-impregnated bone grafts, sampled prior to application in the patient, delivered antibiotics in the concentration ranges of 730–9,800 mg/L for tobramycin and 1,300–11,000 mg/L for vancomycin. Samples taken after application in the patient released lower concentrations of tobramycin (490–1,900 mg/L; P < 0.01) and vancomycin (3,000–5,100 mg/L; P < 0.05); however, these concentrations remained well above the tobramycin minimum inhibitory concentrations (MICs) for investigated, highly tobramycin-resistant Staphylococcus epidermidis strains (MICs > 256 mg/L). At the tested concentrations, bone graft material mixed with TobraVanc delivered antibiotics in potent concentrations above the MICs for bacteria causing PJIs. Clinical trials are needed to evaluate the efficacy and risk of TobraVanc-impregnated bone graft as a prophylactic agent for patients undergoing hip replacement surgery.IMPORTANCEAntibiotic prophylaxis is the cornerstone of successful joint replacement surgery, reducing the risk for the dreaded complication of prosthetic joint infection (PJI) to roughly 0.5%–2% in standard total hip replacement (THR). In addition to systemic antibiotics, antibiotics added locally have the potential to reduce the PJI risk even further, because of the high concentrations that can be achieved in the joint with limited risk for systemic toxicity. The results in the current study show that bone chips impregnated with a combination of tobramycin and vancomycin (TobraVanc) release antibiotics in concentrations that are potent against common bacteria causing PJIs. Especially in high-risk patients, our results support the prophylactic use of TobraVanc in hip replacement surgery requiring the use of a bone graft. A clinical study testing the efficacy of TobraVanc-impregnated bone graft in reducing the incidence of PJI in hip replacement surgery is currently ongoing (EudraCT: 2021-001708-14).

For the Large Hadron Collider luminosity upgrade, two of the NbTi 8.3 T main bending dipoles will be replaced by two shorter Nb3Sn 11.2 T dipoles to create space for the installation of collimators in the dispersion suppression region. With the aim to verify the design features, several 2 m long 11 T models have been constructed and tested at CERN. During the fabrication and assembly of, so far, seven single and two double aperture short model magnets, several challenges were identified and tackled. These include reproducibility in coil fabrication and assembly procedure, as well as control of mechanical stresses in the conductor and surrounding structure. In order to limit coil over-compression and improve reproducibility, the cable insulation was re-optimized. In addition, a review of the collaring procedure of the 11 T magnet was launched with the goal of reducing the risk of conductor degradation due to excessive stress. In this paper, the main fabrication and assembly steps are described, including the description of the actions taken to resolve the identified weakness. [ABSTRACT FROM AUTHOR]

Crucian carp (Carassius carassius), a freshwater fish, can survive chronic anoxia for several months at low temperatures. Consequently, anoxia-related physiological and biochemical adaptations in this species have been studied for more than half a century. Still, despite for the well-known role of protein phosphorylation in regulating cellular processes, no studies have comprehensively characterized the phosphoproteome in crucian carp. In this study, we report the global phosphoproteome in crucian carp brain and liver during anoxia and reoxygenation. By applying a bottom-up proteomic approach on enriched phosphopeptides we found that the brain phosphoproteome shows surprisingly few changes during anoxia-reoxygenation exposure with only 109 out of 4200 phosphopeptides being differentially changed compared to normoxic controls. By contrast, in the liver 395 out of 1287 phosphopeptides changed. Although most changes occurred in the liver phosphoproteome, the pattern of changes indicated metabolic depression and decreased translation in both brain and liver. We also found changes in phosphoproteins involved in apoptotic regulation and reactive oxygen species handling in both tissues. In the brain, some of the most changed phosphopeptides belonged to proteins involved in central nervous system development and neuronal activity at the synaptic cleft. Changed phosphoproteins specific for liver tissue were related to glucose metabolism, such as glycolytic flux and glycogenolysis. In conclusion, protein phosphorylation in response to anoxia and reoxygenation showed both common and tissue-specific changes related to the functional differences between brain and liver.

First principle modeling of the lower hybrid (LH) current drive in tokamak plasmas is a longstanding activity, which is gradually gaining in accuracy thanks to quantitative comparisons with experimental observations. The ability to reproduce simulatenously the plasma current and the non-thermal bremsstrahlung radial profiles in the hard x-ray (HXR) photon energy range represents in this context a significant achievement. Though subject to limitations, ray tracing calculations are commonly used for describing wave propagation in conjunction with Fokker–Planck codes, as it can capture prominent features of the LH wave dynamics in a tokamak plasma-like toroidal refraction. This tool has been validated on several machines when the full absorption of the LH wave requires the transfer of a small fraction of power from the main lobes of the launched power spectrum to a tail at a higher parallel refractive index. Conversely, standard modeling based on toroidal refraction only becomes more challenging when the spectral gap is large, except if other physical mechanisms may dominate to bridge it, like parametric instabilities, as suggested for JET LH discharges (Cesario et al 2004 Phys. Rev. Lett. 92 175002), or fast fluctuations of the launched power spectrum or ‘tail’ LH model, as shown for Tore Supra (Decker et al 2014 Phys. Plasma21 092504). The applicability of the heuristic ‘tail’ LH model is investigated for a broader range of plasma parameters as compared to the Tore Supra study and with different LH wave characteristics. Discrepancies and agreements between simulations and experiments depending upon the different models used are discussed. The existence of a ‘tail’ in the launched power spectrum significantly improves the agreement between modeling and experiments in plasma conditions for which the spectral gap is large in EAST and Alcator C-Mod tokamaks. For the Alcator C-Mod tokamak, the experimental evolution of the HXR profiles with density suggests that this model is valid up to a line-averaged density of m−3, a statement that is confirmed by simulations of the HXR scaling law with density. While simulations with GENRAY/CQL3D codes have ascribed the fast decrease of the HXR emission with density to parasitic absorption in the scrape-off layer by collisional damping, an alternative interpretetation based on an enhanced refraction as the LH wave propagates in the vicinity of the X-point is provided by C3PO/LUKE codes. The consequences for the predictions of LH current in ITER are discussed. [ABSTRACT FROM AUTHOR]

Abstract Treponeme-associated hoof disease (TAHD) is an emerging disease of elk (Cervus canadensis) in the U.S. Pacific West. Because environmental epigenetics is the primary molecular process that mediates environmental factor impacts on a host organism and disease, the role of epigenetics in TAHD etiology was examined. The current study was designed to examine potential effects of TAHD on systemic epigenetic modifications in infected elk over a range of TAHD lesion severity. Leg tendons that contain predominantly fibroblast connective tissue cells were used to isolate fibroblast cells for epigenetic analysis in unaffected and TAHD-positive male and female Roosevelt and Rocky Mountain elk. Differential DNA methylation regions (DMRs) between the unaffected and TAHD-positive elk were identified for both female and male elk. The presence of TAHD was associated with alteration of the connective tissue cell epigenetics, and DMR associated genes identified. Therefore, the infected elk were found to have a systemic epigenetic alteration that was associated with the disease, despite pathology being generally limited to feet. If the elk germline epigenetics is altered then generational transmission of susceptibility to TAHD may impact subsequent generations through epigenetic inheritance. This first study of epigenetic changes associated with disease in elk suggests that TAHD promotes a systemic effect on the elk epigenetics which could exert health impacts on the elk.

The European Union (EU) has underscored its will to heighten its engagement in the Arctic region. Beyond traditional areas of interest – such as tackling climate change, supporting research and developing cooperations – critical resources and security emerged as new topics in the EU’s most recent policy documents. These have become even more critical since February 2022 following Russia’s all-out war against Ukraine. The Circumpolar North is the subject of many challenges caused by climate change and its fragile biodiversity, which, combined with the region’s importance for scientific research, access to natural resources, tourist activities, and military security, places it in a geopolitically strategic position. By focusing on EU ambitions in the Arctic, this article analyses the EU’s potential to implement policies and set consequential trends in an area of political interest outside its jurisdiction. It concludes that core political priorities and sector-specific regulations that directly guide the behaviour of EU members may have more influence than Arctic policy statements.

Runaway electrons can be generated in tokamak plasmas if the accelerating force from the toroidal electric field exceeds the collisional drag force owing to Coulomb collisions with the background plasma. In ITER, disruptions are expected to generate runaway electrons mainly through knock-on collisions (Hender et al 2007 Nucl. Fusion47 S128–202), where enough momentum can be transferred from existing runaways to slow electrons to transport the latter beyond a critical momentum, setting off an avalanche of runaway electrons. Since knock-on runaways are usually scattered off with a significant perpendicular component of the momentum with respect to the local magnetic field direction, these particles are highly magnetized. Consequently, the momentum dynamics require a full 3D kinetic description, since these electrons are highly sensitive to the magnetic non-uniformity of a toroidal configuration. For this purpose, a bounce-averaged knock-on source term is derived. The generation of runaway electrons from the combined effect of Dreicer mechanism and knock-on collision process is studied with the code LUKE, a solver of the 3D linearized bounce-averaged relativistic electron Fokker–Planck equation (Decker and Peysson 2004 DKE: a fast numerical solver for the 3D drift kinetic equation Report EUR-CEA-FC-1736, Euratom-CEA), through the calculation of the response of the electron distribution function to a constant parallel electric field. The model, which has been successfully benchmarked against the standard Dreicer runaway theory now describes the runaway generation by knock-on collisions as proposed by Rosenbluth (Rosenbluth and Putvinski 1997 Nucl. Fusion37 1355–62). This paper shows that the avalanche effect can be important even in non-disruptive scenarios. Runaway formation through knock-on collisions is found to be strongly reduced when taking place off the magnetic axis, since trapped electrons can not contribute to the runaway electron population. Finally, the relative importance of the avalanche mechanism is investigated as a function of the key parameters for runaway electron formation, namely the plasma temperature and the electric field strength. In agreement with theoretical predictions, the LUKE simulations show that in low temperature and electric field the knock-on collisions becomes the dominant source of runaway electrons and can play a significant role for runaway electron generation, including in non-disruptive tokamak scenarios. [ABSTRACT FROM AUTHOR]

Abstract ATP-independent molecular chaperones are important for maintaining cellular fitness but the molecular determinants for preventing aggregation of partly unfolded protein substrates remain unclear, particularly regarding assembly state and basis for substrate recognition. The BRICHOS domain can perform small heat shock (sHSP)-like chaperone functions to widely different degrees depending on its assembly state and sequence. Here, we observed three hydrophobic sequence motifs in chaperone-active domains, and found that they get surface-exposed when the BRICHOS domain assembles into larger oligomers. Studies of loop-swap variants and site-specific mutants further revealed that the biological hydrophobicities of the three short motifs linearly correlate with the efficiency to prevent amorphous protein aggregation. At the same time, they do not at all correlate with the ability to prevent ordered amyloid fibril formation. The linear correlations also accurately predict activities of chimeras containing short hydrophobic sequence motifs from a sHSP that is unrelated to BRICHOS. Our data indicate that short, exposed hydrophobic motifs brought together by oligomerisation are sufficient and necessary for efficient chaperone activity against amorphous protein aggregation.

The Svalbard Archipelago has experienced a rapid increase in tourism-related activities over the past few decades. The Norwegian Government’s ambition to develop the Archipelago’s tourism industry offers multiple socio-economic opportunities. The development and scope of these tourism activities is affected by a complex governance system that entails strict environmental regulation and preparedness considerations. To understand the balance of goals across the national and international policy levels, we have mapped, reviewed, and analyzed the national and international regulations and agreements that affect tourism activities on Svalbard. The document analysis reveals the framework of natural and environmental consideration, access to areas and passage, requirements for organized outdoor activities, and regulatory tools. We discovered conflicts and internal inconsistencies in the way that Svalbard tourism has developed. It has been shaped by both economic growth and environmental preservation, without any specific business development objectives and goals or acceptable limits of environmental and social change in place. For tourism stakeholders, this might complicate any rational assessment of the balance between economic development and environmental status. The challenges we have identified are specific to Svalbard, but are likely to be similar in many other Arctic locations involved in tourism.

Abstract An epigenome-wide association study (EWAS) was performed on buccal cells from monozygotic-twins (MZ) reared together as children, but who live apart as adults. Cohorts of twin pairs were used to investigate associations between neighborhood walkability and objectively measured physical activity (PA) levels. Due to dramatic cellular epigenetic sex differences, male and female MZ twin pairs were analyzed separately to identify differential DNA methylation regions (DMRs). A priori comparisons were made on MZ twin pairs discordant on body mass index (BMI), PA levels, and neighborhood walkability. In addition to direct comparative analysis to identify specific DMRs, a weighted genome coexpression network analysis (WGCNA) was performed to identify DNA methylation sites associated with the physiological traits of interest. The pairs discordant in PA levels had epigenetic alterations that correlated with reduced metabolic parameters (i.e., BMI and waist circumference). The DNA methylation sites are associated with over fifty genes previously found to be specific to vigorous PA, metabolic risk factors, and sex. Combined observations demonstrate that behavioral factors, such as physical activity, appear to promote systemic epigenetic alterations that impact metabolic risk factors. The epigenetic DNA methylation sites and associated genes identified provide insight into PA impacts on metabolic parameters and the etiology of obesity.

Influenza A virus (IAV) is an important human respiratory pathogen that causes significant seasonal epidemics and potential devastating pandemics. As part of its life cycle, IAV encodes the multifunctional protein NS1, that, among many roles, prevents immune detection and limits interferon (IFN) production. As distinct host immune pathways exert different selective pressures against IAV, as replication progresses, we expect a prioritization in the host immune antagonism by NS1. In this work, we profiled bulk transcriptomic differences in a primary bronchial epithelial cell model facing IAV infections at distinct NS1 levels. We further demonstrated that, at single cell level, the intracellular amount of NS1 in-part shapes the heterogeneity of the host response. We found that modulation of NS1 levels reveal a ranking in its inhibitory roles: modest NS1 expression is sufficient to inhibit immune detection, and thus the expression of pro-inflammatory cytokines (including IFNs), but higher levels are required to inhibit IFN signaling and ISG expression. Lastly, inhibition of chaperones related to the unfolded protein response requires the highest amount of NS1, often associated with later stages of viral replication. This work demystifies some of the multiple functions ascribed to IAV NS1, highlighting the prioritization of NS1 in antagonizing the different pathways involved in the host response to IAV infection.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, drastically modifies infected cells to optimize virus replication. One such modification is the activation of the host p38 mitogen-activated protein kinase (MAPK) pathway, which plays a major role in inflammatory cytokine production, a hallmark of severe COVID-19. We previously demonstrated that inhibition of p38/MAPK activity in SARS-CoV-2-infected cells reduced both cytokine production and viral replication. Here, we combined quantitative genetic screening, genomics, proteomics, and phosphoproteomics to better understand mechanisms underlying the dependence of SARS-CoV-2 on the p38 pathway. We found that p38β is a critical host factor for SARS-CoV-2 replication in multiple relevant cell lines and that it functions at a step after viral mRNA expression. We identified putative host and viral p38β substrates in the context of SARS-CoV-2 infection and found that most host substrates have intrinsic antiviral activities. Taken together, this study reveals a unique proviral function for p38β and supports exploring p38β inhibitor development as a strategy toward creating a new class of COVID-19 therapies. IMPORTANCE SARS-CoV-2 is the causative agent of the COVID-19 pandemic that has claimed millions of lives since its emergence in 2019. SARS-CoV-2 infection of human cells requires the activity of several cellular pathways for successful replication. One such pathway, the p38 MAPK pathway, is required for virus replication and disease pathogenesis. Here, we applied systems biology approaches to understand how MAPK pathways benefit SARS-CoV-2 replication to inform the development of novel COVID-19 drug therapies.

In the infrared wavelength region, thermopiles are an important type of detector. A major advantage of thermopiles is their non-cooling requirement. Depending on the applied absorption layer, their responsivity is often rather flat within a large wavelength region. This work presents the fabrication and characterization of a sensitivity and design optimized thermopile detector with a 4 um self-supported SiO2/SU-8 membrane. The structure consists of 240 series interconnected thermocouple junctions obtained by metal evaporation and lift-off. Two metal combinations have been evaluated, namely, nickel/titanium and aluminium/bismuth. Series resistances of 76 kO and 283 kO were measured for the Ni/Ti thermopile and the Al/Bi thermopile respectively. For the Al/Bi thermopile a responsivity of 60 V W[?]1 was achieved using a 1.56 um fibre coupled diode laser with a power of 3.5 mW. Using a white light source with a radiation flux of 0.45 W mm[?]2 a voltage response of 68 V mm2 W[?]1 was measured for the Al/Bi thermopile. The time constant of the characterized detectors was calculated to be 70 ms, using the pulsed IR laser. [ABSTRACT FROM AUTHOR]

Abstract Background Mining can directly and indirectly affect social and environmental systems in a range of positive and negative ways, and may result in societal benefits, but may also cause conflicts, not least in relation to land use. Mining always affects the environment, whilst remediation and mitigation efforts may effectively ameliorate some negative environmental impacts. Social and environmental systems in Arctic and boreal regions are particularly sensitive to impacts from development for numerous reasons, not least of which are the reliance of Indigenous peoples on subsistence livelihoods and long recovery times of fragile ecosystems. With growing metal demand, mining in the Arctic is expected to increase, demanding a better understand its social and environmental impacts. We report here the results of a systematic mapping of research evidence of the impacts of metal mining in Arctic and boreal regions. Methods We searched multiple bibliographic databases and organisational websites for relevant research using tested search strategies. We also collected evidence from stakeholders and rightsholders identified in the wider 3MK project (Mapping the impacts of Mining using Multiple Knowledges, https://osf.io/cvh3u ). We screened articles at three stages (title, abstract, and full text) according to a predetermined set of inclusion criteria, with consistency checks between reviewers at each level. We extracted data relating to causal linkages between actions or impacts and measured outcomes, along with descriptive information about the articles and studies. We have produced an interactive database along with interactive visualisations, and identify knowledge gaps and clusters using heat maps. Review findings Searches identified over 32,000 potentially relevant records, which resulted in a total of 585 articles being retained in the systematic map. This corresponded to 902 lines of data on impact or mitigation pathways. The evidence was relatively evenly spread across topics, but there was a bias towards research in Canada (35% of the evidence base). Research was focused on copper (23%), gold (18%), and zinc (16%) extraction as the top three minerals, and open pit mines were most commonly studied (33%). Research most commonly focused on operation stages, followed by abandonment and post-closure, with little evidence on early stages (prospecting, exploration, construction; 2%), expansion (0.2%), or decommissioning/closure (0.3%). Mitigation measures were not frequently studied (18% articles), with groundwater mitigation most frequently investigated (54% of mitigations), followed by soil quality (12%) and flora species groups (10%). Control-impact study designs were most common (68%) with reference sites as the most frequently used comparator (43%). Only 7 articles investigated social and environmental outcomes together. the most commonly reported system was biodiversity (39%), followed by water (34%), societies (20%), and soil/geology (6%), with air the least common (1%). Conclusions The evidence found highlights a suite of potential knowledge gaps, namely: on early stages prior to operation; effectiveness of mitigation measures; stronger causal inference study designs; migration and demography; cumulative impacts; and impacts on local and Indigenous communities. We also tentatively suggest subtopics where the number of studies could allow systematic reviews: operation, post-closure, and abandonment stages; individual faunal species, surface water quality, water sediment quality; and, groundwater mitigation measure effectiveness.

Abstract Environmental toxicants have been shown to promote the epigenetic transgenerational inheritance of disease through exposure specific epigenetic alterations in the germline. The current study examines the actions of hydrocarbon jet fuel, dioxin, pesticides (permethrin and methoxychlor), plastics, and herbicides (glyphosate and atrazine) in the promotion of transgenerational disease in the great grand-offspring rats that correlates with specific disease associated differential DNA methylation regions (DMRs). The transgenerational disease observed was similar for all exposures and includes pathologies of the kidney, prostate, and testis, pubertal abnormalities, and obesity. The disease specific DMRs in sperm were exposure specific for each pathology with negligible overlap. Therefore, for each disease the DMRs and associated genes were distinct for each exposure generational lineage. Observations suggest a large number of DMRs and associated genes are involved in a specific pathology, and various environmental exposures influence unique subsets of DMRs and genes to promote the transgenerational developmental origins of disease susceptibility later in life. A novel multiscale systems biology basis of disease etiology is proposed involving an integration of environmental epigenetics, genetics and generational toxicology.

ABSTRACT: Objectives: The global increase in carbapenem-resistant Enterobacteriaceae (CRE) is a growing health concern. Infections caused by CRE are associated with increased mortality and length of hospital stay, emphasising the health and economic burden posed by these pathogens. Although CRE can inhabit the human gut asymptomatically, colonisation with CRE is associated with an increased risk of CRE infection and mortality. In this study, we investigated the occurrence and characteristics of CRE in faecal samples from healthy persons in 12 villages in Shandong Province, China. Methods: Screening for CRE in faecal samples was performed by selective cultivation. Minimum inhibitory concentrations (MICs) of meropenem were determined by the agar dilution method. Multilocus sequence typing (MLST) and carbapenemase gene carriage of the isolates were determined by whole-genome sequencing. Genetic relatedness of Escherichia coli isolates was determined by core genome MLST. Results: CRE carriage increased from 2.4% in 2015 to 13.4% in 2017. Most CRE isolates (93.0%) were E. coli and all carried NDM-type carbapenemases. Sequence types (STs) among the E. coli isolates were diverse. The single most common ST was the highly epidemic strain ST167, which was only observed in 2017. Conclusion: We report a rapid increase in occurrence of CRE (from 2.4% to 13.4%) among faecal samples collected from healthy rural residents of Shandong Province from 2015 to 2017. Colonisation with CRE is known to increase the risk of CRE infection, and the worrying deterioration of the epidemiological situation in the region reported here indicates a need for further monitoring and possible interventions.

The crucian carp (Carassius carassius) can survive complete oxygen depletion (anoxia) for several months at low temperatures, making it an excellent model for studying molecular adaptations to anoxia. Still, little is known about how its global proteome responds to anoxia and reoxygenation. By applying mass spectrometry-based proteome analyses on brain, heart and liver tissue from crucian carp exposed to normoxia, five days anoxia, and reoxygenation, we found major changes in particularly cardiac and hepatic protein levels in response to anoxia and reoxygenation. These included tissue-specific differences in mitochondrial proteins involved in aerobic respiration and mitochondrial membrane integrity. Enzymes in the electron transport system (ETS) decreased in heart and increased massively in liver during anoxia and reoxygenation but did not change in the brain. Importantly, the data support a special role for the liver in succinate handling upon reoxygenation, as suggested by a drastic increase of components of the ETS and uncoupling protein 2, which could allow for succinate metabolism without excessive formation of reactive oxygen species (ROS). Also during reoxygenation, the levels of proteins involved in the cristae junction organization of the mitochondria changed in the heart, possibly functioning to suppress ROS formation. Furthermore, proteins involved in immune (complement) system activation changed in the anoxic heart compared to normoxic controls. The results emphasize that responses to anoxia are highly tissue-specific and related to organ function.

Abstract Genetics (i.e., mutations) has been assumed to be the major factor in rheumatoid arthritis (RA) etiology, but accounts for a minority of the variance in disease risk for RA. In contrast to genetics, the environment can have dramatic impacts on epigenetics that associate with disease etiology. The current study used buccal cells and purified blood monocytes from two different clinical cohorts involving Caucasian or African American female populations with or without arthritis. The differential DNA methylation regions (DMRs) between the control and RA populations were identified with an epigenome-wide association study. The DMRs (i.e., epimutations) identified in the buccal cells and monocytes were found to be distinct. The DMR associated genes were identified and many have previously been shown to be associated with arthritis. Observations demonstrate DNA methylation epimutation RA biomarkers are cell type specific and similar findings were observed with the two racial background populations. Rheumatoid arthritis susceptibility epigenetic diagnosis appears feasible and may improve the clinical management of RA and allowpreventative medicine considerations.

Abstract Background The increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) is a growing problem globally, particularly in low- to middle-income countries (LMICs). Previous studies have shown high rates of CRE colonisation among patients at hospitals in LMICs, with increased risk of hospital-acquired infections. Methods We isolated carbapenem-resistant Klebsiella pneumoniae (CRKP) from faecal samples collected in 2017 from patients at admission and discharge at a Vietnamese neonatal intensive care unit (NICU). 126 CRKP were whole-genome sequenced. The phylogenetic relationship between the isolates and between clinical CRKP isolates collected in 2012–2018 at the same hospital were investigated. Results NDM-type carbapenemase-(61%) and KPC-2-encoding genes (41%) were the most common carbapenem resistance genes observed among the admission and discharge isolates. Most isolates (56%) belonged to three distinct clonal clusters of ST15, carrying bla KPC-2, bla NDM-1 and bla NDM-4, respectively. Each cluster also comprised clinical isolates from blood collected at the study hospital. The most dominant ST15 clone was shown to be related to isolates collected from the same hospital as far back as in 2012. Conclusions Highly resistant CRKP were found colonising admission and discharge patients at a Vietnamese NICU, emphasising the importance of continued monitoring. Whole-genome sequencing revealed a population of CRKP consisting mostly of ST15 isolates in three clonally related clusters, each related to blood isolates collected from the same hospital. Furthermore, clinical isolates collected from previous years (dating back to 2012) were shown to likely be clonally descended from ST15 isolates in the largest cluster, suggesting a successful hospital strain which can colonise inpatients.

The herbicide glyphosate has been shown to promote the epigenetic transgenerational inheritance of pathology and disease in subsequent great-grand offspring (F3 generation). This generational toxicology suggests the impacts of environmental exposures need to assess subsequent generations. The current study was designed to identify epigenetic biomarkers for glyphosate-induced transgenerational diseases using an epigenome-wide association study (EWAS). Following transient glyphosate exposure of gestating female rats (F0 generation), during the developmental period of gonadal sex determination, the subsequent transgenerational F3 generation, with no direct exposure, were aged to 1 year and animals with specific pathologies identified. The pathologies investigated included prostate disease, kidney disease, obesity, and presence of multiple disease. The sperm were collected from the glyphosate lineage males with only an individual disease and used to identify specific differential DNA methylation regions (DMRs) and the differential histone retention sites (DHRs) associated with that pathology. Unique signatures of DMRs and DHRs for each pathology were identified for the specific diseases. Interestingly, at a lower statistical threshold overlapping sets of DMRs and DHRs were identified that were common for all the pathologies. This is one of the first observations that sperm histone retention can potentially act as a biomarker for specific diseases. The DMR and DHR associated genes were identified and correlated with known pathology specific-associated genes. Observations indicate transgenerational epigenetic biomarkers of disease pathology can be identified in the sperm that appear to assess disease susceptibility. These biomarkers suggest epigenetic diagnostics could potentially be used to facilitate preventative medicine.