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Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism. Ethanol undergoes a phase I type of reaction, mainly catalyzed by the cytoplasmic enzyme, alcohol dehydrogenase (ADH), and by the microsomal ethanol-oxidizing system (MEOS). Reactive oxygen species (ROS) generated by cytochrome (CYP) 2E1 activity and MEOS contribute to ethanol-induced toxicity. We aimed to: (1) Describe the cellular, pathophysiological and clinical effects of alcohol misuse on the liver; (2) Select the biomarkers and analytical methods utilized by the clinical laboratory to assess alcohol exposure; (3) Provide therapeutic ideas to prevent/reduce alcohol-induced liver injury; (4) Provide up-to-date knowledge regarding the Corona virus and its affect on the liver; (5) Link rare diseases with alcohol consumption. The current review contributes to risk identification of patients with alcoholic, as well as non-alcoholic, liver disease and metabolic syndrome. Additional prevalence of ethnic, genetic, and viral vulnerabilities are presented.
Temperate forests are increasingly subject to natural disturbance by stand replacing windthrows or bark-beetle attacks. Forests are commonly salvage logged after disturbance, whereby substantial parts of biological legacies, such as surviving trees and deadwood, are removed. Despite increasing concerns about the ecological consequences of salvage logging operations, our knowledge on the effects on the soil microbiome and associated functioning remains limited.
Here, we studied soil fungal communities, decomposition processes, and soil organic matter dynamics in 21 intact or disturbed, temperate Norway spruce stands about one decade after they were damaged by windthrow or bark-beetle attacks. Disturbed stands comprised different post-disturbance management, i.e. deadwood retention and salvage logged plots. We used high-throughput sequencing and ergosterol measurements to explore fungal communities and biomass, and enzyme assays to study decomposition processes.
Disturbance shifted soil fungal communities from ectomycorrhizal to saprotrophic dominated assemblages. Fungal biomass declined with decreasing tree abundance after disturbance. Activities of organic matter degrading enzymes declined by ca. 30–80% after disturbance. The relative abundance of ectomycorrhizal fungi was positively related to enzymatic activities. Tree biomass parameters and amounts of deadwood retained were positively related to fungal biomass, certain ectomycorrhizal taxa, and relative ectomycorrhizal fungal abundance among disturbed stands, which, in turn, was associated with higher enzymatic activities.
Our findings demonstrate a significant response of soil fungal communities to natural forest disturbance and salvage logging, with consequences for decomposition and soil organic matter dynamics. We conclude that the retention of surviving trees and deadwood as biological legacies attenuated associated changes to a significant extent, highlighting their importance for the preservation of ectomycorrhizal fungi and the maintenance of decomposition processes after disturbance.
Growing up in cities is associated with increased risk for developing mental health problems. Stress exposure and altered stress regulation have been proposed as mechanisms linking urbanicity and psychopathology, with most research conducted in adult populations. Here, we focus on early childhood, and investigate urbanicity, behavior problems and the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, a central circuit of the stress system, in a sample of N = 399 preschoolers aged 45 months. Urbanicity was coded dichotomously distinguishing between residences with more or less than 100,000 inhabitants. Behavior problems were measured using the Child Behavior Checklist (CBCL) 1½ - 5. Cortisol stress reactivity was assessed using an age-appropriated game-like stress task, and cortisol in the first morning urine was measured to assess nocturnal HPA axis activity. Urbanicity was not associated with behavior problems, urinary cortisol or the cortisol stress response. Neither urinary cortisol nor salivary cortisol response after stress exposure were identified as mediators of the relationship between urbanicity and behavior problems. The findings suggest no strong association of urbanicity with behavior problems and HPA axis regulation in preschool age. To our knowledge, this is the youngest sample to date studying the relationship between urbanicity and behavior problems as well as HPA axis regulation. Future research should examine at which age associations can first be identified and which mechanisms contribute to these relationships.
Aim
To compare overall mortality (OM), cancer-specific mortality (CSM), and other cause mortality (OCM) rates between radical prostatectomy (RP) versus radiotherapy (RT) in clinical node-positive (cN1) prostate cancer (PCa).
Materials and Methods
Within Surveillance, Epidemiology, End Results (SEER) (2004–2016), we identified 4685 cN1 PCa patients, of whom 3589 (76.6%) versus 1096 (24.4%) were treated with RP versus RT. After 1:1 propensity score matching (PSM), Kaplan–Meier plots and Cox regression models tested the effect of RP versus RT on OM, while cumulative incidence plots and competing-risks regression (CRR) models addressed CSM and OCM between RP and RT patients. All analyses were repeated after the inverse probability of treatment weighting (IPTW). For CSM and OCM analyses, the propensity score was used as a covariate in the regression model.
Results
Overall, RT patients were older, harbored higher prostate-specific antigen values, higher clinical T and higher Gleason grade groups. PSM resulted in two equally sized groups of 894 RP versus 894 RT patients. After PSM, 5-year OM, CSM, and OCM rates were, respectively, 15.4% versus 25%, 9.3% versus 17%, and 6.1% versus 8% for RP versus RT (all p < 0.001) and yielded respective multivariate hazard ratios (HRs) of 0.63 (0.52–0.78, p < 0.001), 0.66 (0.52–0.86, p < 0.001), 0.71 (0.5–1.0, p = 0.05), all favoring RP. After IPTW, Cox regression models yielded HR of 0.55 (95% confidence interval [CI] = 0.46–0.66) for OM, and CRR yielded HRs of 0.49 (0.34–0.70) and 0.54 (0.36–0.79) for, respectively, CSM and OCM, all favoring RP (all p < 0.001).
Conclusions
RP may hold a CSM advantage over RT in cN1 PCa patients.
The intensity and the features of sensory stimuli are encoded in the activity of neurons in the cortex. In the visual and piriform cortices, the stimulus intensity rescales the activity of the population without changing its selectivity for the stimulus features. The cortical representation of the stimulus is therefore intensity invariant. This emergence of network-invariant representations appears robust to local changes in synaptic strength induced by synaptic plasticity, even though (i) synaptic plasticity can potentiate or depress connections between neurons in a feature-dependent manner, and (ii) in networks with balanced excitation and inhibition, synaptic plasticity determines the nonlinear network behavior. In this study we investigate the consistency of invariant representations with a variety of synaptic states in balanced networks. By using mean-field models and spiking network simulations, we show how the synaptic state controls the emergence of intensity-invariant or intensity-dependent selectivity. In particular, we demonstrate that an effective power-law synaptic transformation at the population level is necessary for invariance. In a range of firing rates, purely depressing short-term synapses fulfills this condition, and in this case, the network is contrast-invariant. Instead, facilitating short-term plasticity generally narrows the network selectivity. We found that facilitating and depressing short-term plasticity can be combined to approximate a power-law that leads to contrast invariance. These results explain how the physiology of individual synapses is linked to the emergence of invariant representations of sensory stimuli at the network level.
A plethora of modified nucleotides extends the chemical and conformational space for natural occurring RNAs. tRNAs constitute the class of RNAs with the highest modification rate. The extensive modification modulates their overall stability, the fidelity and efficiency of translation. However, the impact of nucleotide modifications on the local structural dynamics is not well characterized. Here we show that the incorporation of the modified nucleotides in tRNAfMet from Escherichia coli leads to an increase in the local conformational dynamics, ultimately resulting in the stabilization of the overall tertiary structure. Through analysis of the local dynamics by NMR spectroscopic methods we find that, although the overall thermal stability of the tRNA is higher for the modified molecule, the conformational fluctuations on the local level are increased in comparison to an unmodified tRNA. In consequence, the melting of individual base pairs in the unmodified tRNA is determined by high entropic penalties compared to the modified. Further, we find that the modifications lead to a stabilization of long-range interactions harmonizing the stability of the tRNA’s secondary and tertiary structure. Our results demonstrate that the increase in chemical space through introduction of modifications enables the population of otherwise inaccessible conformational substates.
Research in social insects has shown that hydrocarbons on their cuticle are species-specific. This has also been proven for Diptera and is a promising tool for identifying important fly taxa in Forensic Entomology. Sometimes the empty puparia, in which the metamorphosis to the adult fly has taken place, can be the most useful entomological evidence at the crime scene. However, so far, they are used with little profit in criminal investigations due to the difficulties of reliably discriminate among different species. We analysed the CHC chemical profiles of empty puparia from seven forensically important blow flies Calliphora vicina, Chrysomya albiceps, Lucilia caesar, Lucilia sericata, Lucilia silvarum, Protophormia terraenovae, Phormia regina and the flesh fly Sarcophaga caerulescens. The aim was to use their profiles for identification but also investigate geographical differences by comparing profiles of the same species (here: C. vicina and L. sericata) from different regions. The cuticular hydrocarbons were extracted with hexane and analysed using gas chromatography-mass spectrometry. Our results reveal distinguishing differences within the cuticular hydrocarbon profiles allowing for identification of all analysed species. There were also differences shown in the profiles of C. vicina from Germany, Spain, Norway and England, indicating that geographical locations can be determined from this chemical analysis. Differences in L. sericata, sampled from England and two locations in Germany, were less pronounced, but there was even some indication that it may be possible to distinguish populations within Germany that are about 70 km apart from one another.
With the introduction of the virtual allocation crossmatch in the Eurotransplant (ET) region in 2023, the determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients is of utmost importance for histocompatibility laboratories and transplant centers. Therefore, a joined working group of members from the German Society for Immunogenetics (Deutsche Gesellschaft für Immungenetik, DGI) and the German Transplantation Society (Deutsche Transplantationsgesellschaft, DTG) revised and updated the previous recommendations from 2015 in light of recently published evidence. Like in the previous version, a wide range of topics is covered from technical issues to clinical risk factors. This review summarizes the evidence about the prognostic value of contemporary methods for HLA antibody detection and identification, as well as the impact of UAM on waiting time, on which these recommendations are based. As no clear criteria could be determined to differentiate potentially harmful from harmless HLA antibodies, the general recommendation is to assign all HLA against which plausible antibodies are found as UAM. There is, however, a need for individualized solutions for highly immunized patients. These revised recommendations provide a list of aspects that need to be considered when assigning UAM to enable a fair and comprehensible procedure and to harmonize risk stratification prior to kidney transplantation between transplant centers.
Mining is one of the major pollution sources worldwide, causing huge disturbances to the environment. Industrial and artisanal mining activities are widespread in Mexico, a major global producer of various metals. This study aimed to assess the ecological impairments resulting from mining activities using aquatic macroinvertebrates assemblages (MA). A multiple co-inertia analysis was applied to determine the relationships between environmental factors, habitat quality, heavy metals, and aquatic macroinvertebrates in 15 study sites in two different seasons (dry and wet) along two rivers running across the Central Plateau of Mexico. The results revealed three contrasting environmental conditions associated with different MAs. High concentrations of heavy metals, nutrients, and salinity limit the presence of several families of seemingly sensitive macroinvertebrates. These factors were found to influence structural changes in MAs, showing that not only mining activities, but also agriculture and presence of villages in the basin, exert adverse effects on macroinvertebrate assemblages. Diversity indices showed that the lowest diversity matched both the most polluted and the most saline rivers. The rivers studied displayed high alkalinity and hardness levels, which can reduce the availability of metals and cause adverse effects on periphyton by inhibiting photosynthesis and damaging MAs. Aquatic biomonitoring in rivers, impacted by mining and other human activities, is critical for detecting the effect of metals and other pollutants to improve management and conservation strategies. This study supports the design of cost-effective and accurate water quality biomonitoring protocols in developing countries.
The Indian species of the genera Orionis Shaw and Stenothremma Shaw (Braconidae, Euphorinae) are reviewed. Both genera are reported for the first time from India. Three new species, Orionis shillongensis Gupta, van Achterberg & Pattar sp. nov. from north-eastern India (Meghalaya), O. femorator Gupta, van Achterberg & Pattar sp. nov. from southern India (Karnataka and Tamil Nadu) and Stenothremma flavator Gupta & van Achterberg sp. nov. from southern India (Karnataka) are illustrated and described. A key to the Old World species of Orionis Shaw is provided.