Occurrence of double-stranded RNA species in champignon and their relation to Mushroom Virus X symptoms

Mycoviruses are known to infect fungi of different habitats and life style. Some of them, like the Mushroom Virus X (MVX) complex, cause abnormal development of fruiting bodies and severe yield losses in mushroom cultivation. Most mycoviruses have a double-stranded RNA (dsRNA) genome, therefore dsRNA-detection is frequently used as a first step to identify virus infection. In relation with MVX 23 dsRNAs species have been described, occurring in variable number and combination in diseased mushrooms. The aim of our experiments was to find out whether dsRNA-immunoblotting can be used to detect dsRNA in small samples of cultivated A. bisporus varieties and of wild growing Agaricus species. We found that by immunoblotting, the same dsRNA species were detected in apparently healthy cultivated champignon fruiting bodies and in MVX-infected reference samples, respectively, as by conventional CF11 chromatography, but for immunoblotting a much smaller sample size was needed. In two out of three deformed fruit bodies of cultivated A. bisporus from Hungary we detected a 4.1 kbp dsRNA species which was also present in the MVX infected reference samples. Diverse and variable dsRNA patterns were observed in apparently healthy samples of 12 wild growing Agaricus species, indicating that extreme care should be taken when non-cultivated Agaricus is used for breeding new varieties. Non-sterile cultures and environmental mushroom specimens are fairly often mixed with parasitic and endofungal organisms, therefore, we also tested fungi isolated from mushroom cultures. Here again, 1–7 dsRNA species were found in extracts of Trichoderma and Dactylium isolates and of Mycogone-infected sporophores. Our results demonstrate clearly that dsRNAs from very different origins can be present in cultivated champignon and support the view that the MVX symptom-associated dsRNAs are probably of polyphyletic origin and do not represent one defined virus

Leaf water δ 18/O, δ2H and d-excess isoscapes for Australia using region-specific plant parameters and non-equilibrium vapour

Oxygen (δ18O) and hydrogen (δ2H) isotope ratios, and their relationship to one another (d-excess) are altered as water travels from the atmosphere to the land surface, into soils and plants and back to the atmosphere. Plants return water to the atmosphere through transpiration (evaporation through the stomata), which causes isotopic fractionation concentrating the heavier isotopes (18O and 2H) in the water that remains behind in the leaves. The degree of isotopic fractionation during transpiration is controlled largely by climate, and as a result can be predicted using process-based models and climate data. The modelled transpirational isotopic fractionation can be applied to plant source water isotopic values to predict leaf water isotope ratios and generate maps of isotopic composition, or isoscapes. This approach of mechanistic modelling has been well demonstrated in the first generation of global leaf water isoscapes (PLoS One, 3(6), e2447, 2008). However, use of leaf water isoscapes in fields such as hydrology, ecology, and forensics requires a new generation of updated region-specific isoscapes. Here, we generate leaf water isoscapes of δ18O, δ2H and d-excess for Australia, the driest vegetated continent on Earth, where leaf water represents a critical water resource for ecosystems. These isoscapes represent an improvement over previous global isoscapes due to their higher resolution, region-specific, empirically derived plant parameters, and non-equilibrium corrections for water vapour isotopic composition. The new isoscapes for leaf water are evaluated relative to observed isotope ratios of leaf cellulose and cherry juice. The model predictions for annual average leaf water isotope ratios showed strong correlations with these plant tissues that integrate over time. Moreover, inclusion of region-specific leaf temperature estimates and non-equilibirum vapour corrections improved prediction accuracy. Regionally based isoscapes provide improved characterisations of average leaf water isotope ratios needed to support research in hydrology, plant ecophysiology, atmospheric science, ecology, and geographic provenancing of biological materials

Survival and longevity of European rulers: geographical influences and exploring potential factors, including the Mediterranean diet - a historical analysis from 1354 to the twentieth century

Significant regional variability in lifespan in Europe is influenced by environmental factors and lifestyle behaviors, including diet. This study investigates the impact of geographical region on the lifespan of European rulers spanning from the fourteenth century to the present day. By analyzing historical records and literature, we aim to identify region-specific dietary patterns and lifestyle factors that may have contributed to longer lifespans among rulers. The hypothesis to be tested is that rulers from Southern European countries, where the traditional Mediterranean diet is consumed by the local people, may exhibit longer lifespans compared to rulers from other regions, due to the well-documented health benefits associated with this dietary pattern. We extracted comprehensive information for each ruler, encompassing their sex, birth and death dates, age, age of enthronement, duration of rulership, country, and cause of death (natural vs. non-natural). To determine their nationality, we coded rulers based on their hypothetical present-day residence (2023). Utilizing the EuroVoc Geographical classification, we categorized the countries into four regions: Northern, Western, Southern, Central and Eastern Europe. While Cox regression models did not find significant differences in survival rates among regions, further analysis stratified by time periods revealed intriguing trends. Contrary to our initial predictions, the Northern region displayed better survival rates compared to the Southern region between 1354 and 1499, whereas survival rates were similar across regions from 1500 to 1749. However, after 1750, all regions, except the Southern region, exhibited significantly improved survival rates, suggesting advancements in healthcare and lifestyle factors. These findings underscore the dynamic influence of both region and time period on health and longevity. Interestingly, despite the prevalence of the Mediterranean diet in the Southern region of Europe, rulers from this region did not demonstrate longer lifespans compared to their counterparts in other regions. This suggests that additional lifestyle factors may have played a more prominent role in their longevity. In conclusion, our study sheds light on the intricate relationship between region, time period, and lifespan among European rulers. Although the Mediterranean diet is often associated with health benefits, our findings indicate that it alone may not account for differences in ruler longevity across regions. Further research is warranted to explore the impact of other lifestyle factors on the health and lifespan of European rulers throughout history

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age-related diseases affecting the cardiovascular system and central nervous system is discussed, with a specific focus on Alzheimer’s disease, Parkinson’s disease, stroke, small vessel disease, and vascular cognitive impairment (VCI). Aging is a major risk factor for these diseases. Their pathogenesis involves cellular and molecular mechanisms of aging such as increased oxidative stress, impaired mitochondrial function, DNA damage, and inflammation and is influenced by environmental factors. Environmental toxicants, including ambient particulate matter, pesticides, heavy metals, and organic solvents, have been identified as significant contributors to cardiovascular and brain aging disorders. These toxicants can inflict both macro- and microvascular damage and many of them can also cross the blood–brain barrier, inducing neurotoxic effects, neuroinflammation, and neuronal dysfunction. In conclusion, environmental factors play a critical role in modulating cardiovascular and brain aging. A deeper understanding of how environmental toxicants exacerbate aging processes and contribute to the pathogenesis of neurodegenerative diseases, VCI, and dementia is crucial for the development of preventive strategies and interventions to promote cardiovascular, cerebrovascular, and brain health. By mitigating exposure to harmful environmental factors and promoting healthy aging, we can strive to reduce the burden of age-related cardiovascular and brain pathologies in the aging population

An improved female-targeted semiochemical lure for the European corn borer Ostrinia nubilalis Hbn.

The addition of synthetic 4-methoxy-2-phenethyl alcohol to the known attractant phenylacetaldehyde synergized attraction of the European corn borer Ostrinia nubilalis, the blend invariably catching 3 to 5 times more than phenylacetaldehyde on its own. Highest catches were recorded by the 1:1 blend. Both females and males were attracted, supposedly in the natural sex ratio of the local population. This improved bisex O. nubilalis attractant could be more efficient and more suitable for detection and monitoring purposes than previously know lures, making possible to draw more reliable plant protection decisions

High-soluble CGA levels are associated with poor survival in bladder cancer

Recently, a neuroendocrine-like molecular subtype has been discovered in muscle-invasive urothelial bladder cancer (BC). Chromogranin A (CGA) is a widely used tissue and serum marker in neuroendocrine tumors. Our aim was to evaluate serum CGA (sCGA) concentrations and their associations with clinical and follow-up data in BC and renal cell carcinoma (RCC). sCGA concentrations were analyzed in the following cohorts: (1) BC training set (n = 188), (2) BC validation set (n = 125), (3) RCC patients (n = 77), (4) healthy controls (n = 97). CGA immunohistochemistry and RT-qPCR analyses were performed in 20 selected FFPE and 29 frozen BC tissue samples. Acquired data were correlated with clinicopathological parameters including comorbidities with known effect on sCGA as well as with patients’ follow-up data. sCGA levels were significantly higher in BC but not in RCC patients compared to healthy controls. High sCGA levels were independently associated with poor overall and disease-specific survival both in the BC training (P < 0.001, P = 0.002) and validation set (P = 0.009, P = 0.017). sCGA levels were inversely correlated with glomerulus filtrating rate (GFR) and linearly correlated with creatinine clearance and urea concentrations. These correlations were not related to the prognostic value of sCGA. Tissue CGA levels were low to absent independently of sCGA concentrations. Our results demonstrate elevated levels and an independent prognostic value for sCGA in BC but not in RCC. Despite the significant correlation between sCGA and GFR, the prognostic relevance of sCGA seems not related to impaired renal function or other comorbidities

EnzyMiner: automatic identification of protein level mutations and their impact on target enzymes from PubMed abstracts

BACKGROUND: A better understanding of the mechanisms of an enzyme's functionality and stability, as well as knowledge and impact of mutations is crucial for researchers working with enzymes. Though, several of the enzymes' databases are currently available, scientific literature still remains at large for up-to-date source of learning the effects of a mutation on an enzyme. However, going through vast amounts of scientific documents to extract the information on desired mutation has always been a time consuming process. In this paper, therefore, we describe an unique method, termed as EnzyMiner, which automatically identifies the PubMed abstracts that contain information on the impact of a protein level mutation on the stability and/or the activity of a given enzyme. RESULTS: We present an automated system which identifies the abstracts that contain an amino-acid-level mutation and then classifies them according to the mutation's effect on the enzyme. In the case of mutation identification, MuGeX, an automated mutation-gene extraction system has an accuracy of 93.1% with a 91.5 F-measure. For impact analysis, document classification is performed to identify the abstracts that contain a change in enzyme's stability or activity resulting from the mutation. The system was trained on lipases and tested on amylases with an accuracy of 85%. CONCLUSION: EnzyMiner identifies the abstracts that contain a protein mutation for a given enzyme and checks whether the abstract is related to a disease with the help of information extraction and machine learning techniques. For disease related abstracts, the mutation list and direct links to the abstracts are retrieved from the system and displayed on the Web. For those abstracts that are related to non-diseases, in addition to having the mutation list, the abstracts are also categorized into two groups. These two groups determine whether the mutation has an effect on the enzyme's stability or functionality followed by displaying these on the web

Ex vivo modelling of drug efficacy in a rare metastatic urachal carcinoma

Background Ex vivo drug screening refers to the out-of-body assessment of drug efficacy in patient derived vital tumor cells. The purpose of these methods is to enable functional testing of patient specific efficacy of anti-cancer therapeutics and personalized treatment strategies. Such approaches could prove powerful especially in context of rare cancers for which demonstration of novel therapies is difficult due to the low numbers of patients. Here, we report comparison of different ex vivo drug screening methods in a metastatic urachal adenocarcinoma, a rare and aggressive non-urothelial bladder malignancy that arises from the remnant embryologic urachus in adults. Methods To compare the feasibility and results obtained with alternative ex vivo drug screening techniques, we used three different approaches; enzymatic cell viability assay of 2D cell cultures and image-based cytometry of 2D and 3D cell cultures in parallel. Vital tumor cells isolated from a biopsy obtained in context of a surgical debulking procedure were used for screening of 1160 drugs with the aim to evaluate patterns of efficacy in the urachal cancer cells. Results Dose response data from the enzymatic cell viability assay and the image-based assay of 2D cell cultures showed the best consistency. With 3D cell culture conditions, the proliferation rate of the tumor cells was slower and potency of several drugs was reduced even following growth rate normalization of the responses. MEK, mTOR, and MET inhibitors were identified as the most cytotoxic targeted drugs. Secondary validation analyses confirmed the efficacy of these drugs also with the new human urachal adenocarcinoma cell line (MISB18) established from the patient’s tumor. Conclusions All the tested ex vivo drug screening methods captured the patient’s tumor cells’ sensitivity to drugs that could be associated with the oncogenic KRASG12V mutation found in the patient’s tumor cells. Specific drug classes however resulted in differential dose response profiles dependent on the used cell culture method indicating that the choice of assay could bias results from ex vivo drug screening assays for selected drug classes