Life

The fish parasite, Neoergasilus japonicus (Harada, 1930), native to Eastern Siberia and the Amur River catchment area, invaded European water bodies in the middle of the last century, possibly due to the human-mediated distribution of fish in the Amur complex (i.e., the genera Hypophthalmichthys and Ctenopharyngodon). In the deep karst lake, Grand Laoucien (Marseille area, France), this species had an unusually high population density (from 1000 ind./ m³ in zooplankton to 4000 ind./ m³ in the nearshore area) during the free-living period of its life cycle. The annual cycle of N. japonicus includes a 5-month overwintering of fertilized females attached to fish fins and, following this, a five- to six-generation chain from March to November, when the free-living stages in the population alternate with parasite females which attach to their hosts for breeding. The population density of the parasites in zooplankton increased exponentially from spring to autumn, which positively correlated with temperature. We found a strong correlation between N. japonicus density and the community development of microphytobenthos, but not between N. japonicus and phyto- or zooplankton dynamics. The local contributing factors included a seasonal three-fold decrease in water levels and the development of anoxia in profundal waters, which led to a high ambient fish density and thus susceptibility to the parasite. Although the free-living parasite represented only 1% of zooplankton production, it consumed up to 25% of small invertebrate productivity. The maximum intensity of infection reached 140 parasites per fish, or 4.14 per g of weight. The high infection of fish with this parasite, in our opinion, indicated the danger it poses to the local ichthyofauna, which first encountered this new parasite. Full article

Wnt family proteins and β-catenin are critical for the regulation of many developmental and oncogenic processes. Wnts are secreted protein ligands which signal using a canonical pathway, and involve the transcriptional co-activator β-catenin or non-canonical pathways that are independent of β-catenin. Bone metastasis is unfortunately a common occurrence in prostate cancer and can be conceptualized as a series of related steps or processes, most of which are regulated by Wnt ligands and/or β-catenin. At the primary tumor site, cancer cells often take on mesenchymal properties, termed epithelial mesenchymal transition (EMT), which are regulated in part by the Wnt receptor FZD4. Then, Wnt signaling, especially Wnt5A, is of importance as the cells circulate in the blood stream. Upon arriving in the bones, cancer cells migrate and take on stem-like or tumorigenic properties, as aided through Wnt or β-catenin signaling involving CHD11, CD24, and Wnt5A. Additionally, cancer cells can become dormant and evade therapy, in part due to regulation by Wnt5A. In the bones, E-selectin can aid in the reversal of EMT, a process termed mesenchymal epithelial transition (MET), as a part of metastatic tumorigenesis. Once bone tumors are established, Wnt/β-catenin signaling is involved in the suppression of osteoblast function largely through DKK1. Full article

In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based on roles in sleep regulation and sensitivity to sleep disruption. For autophagy, we monitored the levels of various autophagic induction markers including beclin1, LC3II, and p62 as well as the levels of lysosomal associated membrane protein 1 and 2 (LAMP1/2) and the transcription factor EB (TFEB) which are critical for lysosome function and autophagy maturation stage. For the status of microglia and astrocytes, we determined the levels of Iba1 and GFAP in these brain regions. We also measured the levels of CRF and its cognate receptors 1 and 2 (CRFR1/2). Our results showed that 5 days of SF dysregulated autophagy in the striatum and hippocampus but not in the frontal cortex. Additionally, 5 days of SF activated microglia in the striatum but not in the hippocampus or frontal cortex. In the striatum, CRFR2 but not CRFR1 was significantly increased in SF-experienced mice. CRF did not alter its mRNA levels in any of the three brain regions assessed. Our findings revealed that autophagy processes are sensitive to short-term SF in a region-specific manner and suggest that autophagy dysregulation may be a primary initiator for brain changes and functional impairments in the context of sleep disturbances and disorders. Full article

The twentieth century witnessed a huge expansion in the number of vaccines used with great success in combating diseases, especially the ones caused by viral and bacterial pathogens. Despite this, several major public health threats, such as HIV, tuberculosis, malaria, and cancer, still pose an enormous humanitarian and economic burden. As vaccines based on the induction of protective, neutralizing antibodies have not managed to effectively combat these diseases, in recent decades, the focus has increasingly shifted towards the cellular immune response. There is substantial evidence demonstrating CD8 T cells as key players in the protection not only against many viral and bacterial pathogens, but also in the fight against neoplastic cells. Here, we present arguments for CD8 T cells to be considered as promising candidates for vaccine targeting. We discuss the heterogeneity of CD8 T cell populations and their contribution in the protection of the host. We also outline several strategies of using a common human pathogen, cytomegalovirus, as a vaccine vector since accumulated data strongly suggest it represents a promising approach to the development of novel vaccines against both pathogens and tumors. Full article

The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5′ to 3′ polarity or 3′ poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer; circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers. Full article

Natural anticoagulant drugs can be obtained from plants, rich in secondary bioactive metabolites which, in addition to being effective antioxidants, also possess anticoagulant and antiplatelet properties and, for this reason, can be excellent candidates for the treatment of thrombotic diseases. This review reports an overview of the hemostatic process and thrombotic disorders together with data on plants, more and less common from around the world, containing bioactive compounds characterized by antiplatelet and anticoagulant activity. The reported literature was obtained from Medline, PubMed, Elsevier, Web of Science, Google Scholar considering only articles in the English language, published in peer-reviewed journals. The number of citations of the articles and the impact factor of the journals were other parameters used to select the scientific papers to be included in the review. The analysis of the literature data selected demonstrates that many plants’ bioactive compounds show antiplatelet and anticoagulant activity that make them potential candidates to be used as new natural compounds able to interfere with both primary and secondary hemostasis. Moreover, they could be used together with anticoagulants currently administered in clinical practice to increase their efficacy and to reduce complications in the treatment of thrombotic disorders. Full article

Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury and acute liver failure. Approximately 10% of APAP is metabolized by cytochrome P450 (CYP2E1) into toxic N-acetyl-p-benzoquinone imine (NAPQI). CYP2E1 also contributes to ethanol metabolism, especially during conditions of high blood ethanol concentration. Acute and chronic ethanol consumption appears to have opposite effects on APAP-induced liver injury. We determined the effects of different doses, pre- and post-treatment, and various schedules of ethanol exposure in APAP-induced liver injury. Treatment with ethanol (0.5 g/kg) after 1 h of APAP (300 mg/kg) administration decreased serum ALT levels, histopathological features, and inflammatory cell infiltration. Moreover, ethanol treatment 1 h after APAP treatment reduced APAP-induced liver injury compared with later administration. Interestingly, ethanol pretreatment did not provide any protective effect. Furthermore, ethanol treatment was associated with a significant decrease in ERK and AKT phosphorylation during the acute injury phase. Ethanol exposure also increased CYP2E1 expression and decreased PCNA expression during the liver regeneration phase. Full article

Many Isaria-like species have recently been moved into more appropriate genera. However, more robust molecular phylogenetic analyses are still required for Isaria-like fungi to ensure accurate taxonomic identification. We analyzed these Isaria-like strains using multi-gene phylogenetics. Cryptic diversity was discovered in several Isaria farinosa strains, and two new species, Samsoniella pseudogunnii and S. pupicola, are proposed. Our results reveal that more attention needs to be paid to cryptic intraspecific diversity across different isolates and genotypes of the Isaria-like species, some of which will need to be transferred to Samsoniella. Interestingly, S. hepiali, with a very broad host distribution, has been widely used as a medicinal and edible cordycipitoid fungus. Full article

Idiopathic pulmonary fibrosis, which is one of the lung diseases, is quite rare but fatal in nature. The disease is progressive, and detection of severity takes a long time as well as being quite tedious. With the advent of intelligent machine learning techniques, and also the effectiveness of these techniques, it was possible to detect many lung diseases. So, in this paper, we have proposed a model that could be able to detect the severity of IPF at the early stage so that fatal situations can be controlled. For the development of this model, we used the IPF dataset of the Korean interstitial lung disease cohort data. First, we preprocessed the data while applying different preprocessing techniques and selected 26 highly relevant features from a total of 502 features for 2424 subjects. Second, we split the data into 80% training and 20% testing sets and applied oversampling on the training dataset. Third, we trained three state-of-the-art machine learning models and combined the results to develop a new soft voting ensemble-based model for the prediction of severity of IPF disease in patients with this chronic lung disease. Hyperparameter tuning was also performed to get the optimal performance of the model. Fourth, the performance of the proposed model was evaluated by calculating the accuracy, AUC, confusion matrix, precision, recall, and F1-score. Lastly, our proposed soft voting ensemble-based model achieved the accuracy of 0.7100, precision 0.6400, recall 0.7100, and F1-scores 0.6600. This proposed model will help the doctors, IPF patients, and physicians to diagnose the severity of the IPF disease in its early stages and assist them to take proactive measures to overcome this disease by enabling the doctors to take necessary decisions pertaining to the treatment of IPF disease. Full article

In order for Man to venture further into Space he will have to adapt to its conditions, including microgravity. Life as we know it has evolved on Earth with a substantial gravitational field. If they spend considerable time away from Earth, astronauts experience physiological, mental, and anatomical changes. It is not clear if these are pathological or adaptations. However, it is true that they experience difficulties on their return to stronger gravity. The cytoskeleton is a key site for the detection of gravitational force within the body, due to its tensegrity architecture. In order to understand what happens to living beings in space, we will need to unravel the role cytoskeletal tensegrity architecture plays in the building and function of cells, organs, the body, and mind. Full article

High quality nucleic acids (with high integrity, purity, and biological activity) have become indispensable products of modern society, both in molecular diagnosis and to be used as biopharmaceuticals. As the current methods available for the extraction and purification of nucleic acids are laborious, time-consuming, and usually rely on the use of hazardous chemicals, there is an unmet need towards the development of more sustainable and cost-effective technologies for nucleic acids purification. Accordingly, this study addresses the preparation and evaluation of silica-based materials chemically modified with chloride-based ionic liquids (supported ionic liquids, SILs) as potential materials to effectively isolate RNAs. The investigated chloride-based SILs comprise the following cations: 1-methyl-3-propylimidazolium, triethylpropylammonium, dimethylbutylpropylammonium, and trioctylpropylammonium. All SILs were synthesized by us and characterized by solid-state ¹³C Nuclear Magnetic Resonance (NMR), Scanning Electron Microscopy (SEM), elemental analysis, and zeta potential measurements, confirming the successful covalent attachment of each IL cation with no relevant changes in the morphology of materials. Their innovative application as chromatographic supports for the isolation of recombinant RNA was then evaluated. Adsorption kinetics of transfer RNA (tRNA) on the modified silica-based materials were investigated at 25 °C. Irrespective to the immobilized IL, the adsorption experimental data are better described by a pseudo first-order model, and maximum tRNA binding capacities of circa 16 µmol of tRNA/g of material were achieved with silica modified with 1-methyl-3-propylimidazolium chloride and dimethylbutylpropylammonium chloride. Furthermore, the multimodal character displayed by SILs was explored towards the purification of tRNA from Escherichia coli lysates, which in addition to tRNA contain ribosomal RNA and genomic DNA. The best performance on the tRNA isolation was achieved with SILs comprising 1-methyl-3-propylimidazolium chloride and dimethylbutylpropylammonium chloride. Overall, the IL modified silica-based materials represent a more efficient, sustainable, and cost-effective technology for the purification of bacterial RNAs, paving the way for their use in the purification of distinct biomolecules or nucleic acids from other sources. Full article

Due to the decline in the population and the difficulty of in situ conservation, several anuran species are being reared in captivity. In this study, we identified physiological and morphological differences between farm-bred and wild frogs. Nine different serum components were used as indicators of osmotic pressure, homeostatic state, organ function, and nutritional status of farm-bred frogs and wild frogs, while radiographic techniques were used to visualize differences in bone mineral density and body composition ratio. Additionally, X-ray skeletal images were used for morphological analysis to estimate differences in locomotory performance between the two groups. Wild frogs harbor traits that aid in better locomotory performance than farm-bred frogs. They also have a relatively lower fat content ratio and higher calcium and phosphorus serum levels than farm-bred frogs, suggesting a difference in nutritional status. However, hepatic stress was higher in wild frogs than in farm-bred frogs. Veterinary clinical examinations allow for the identification of differences in nutritional and morphological conditions between farm-bred and wild frogs. Determining the health of animals can help improve their living conditions, eliminate conditions that can negatively affect them, and effectively manage them on farms, in zoos, and at ex situ conservation institutes. Full article

The establishment of a functional cardiovascular system is crucial for the development of all vertebrates. Defects in the development of the cardiovascular system lead to cardiovascular diseases, which are among the top 10 causes of death worldwide. However, we are just beginning to understand which signaling pathways guide blood vessel growth in different tissues and organs. The advantages of the model organism zebrafish (Danio rerio) helped to identify novel cellular and molecular mechanisms of vascular growth. In this review we will discuss the current knowledge of vasculogenesis and angiogenesis in the zebrafish embryo. In particular, we describe the molecular mechanisms that contribute to the formation of blood vessels in different vascular beds within the embryo. Full article

RNA synthesis inhibitors and protein synthesis inhibitors are useful for investigating whether biological events with unknown mechanisms require transcription or translation; however, the dependence of RNA synthesis has been difficult to verify because many RNA synthesis inhibitors cause adverse events that trigger a p53 response. In this study, we screened a library containing 9600 core compounds and obtained STK160830 that shows anti-apoptotic effects in irradiated wild-type-p53-bearing human T-cell leukemia MOLT-4 cells and murine thymocytes. In many of the p53-impaired cells and p53-knockdown cells tested, STK160830 did not show a remarkable anti-apoptotic effect, suggesting that the anti-apoptotic activity is p53-dependent. In the expression analysis of p53, p53-target gene products, and reference proteins by immunoblotting, STK160830 down-regulated the expression of many of the proteins examined, and the downregulation correlated strongly with its inhibitory effect on cell death. mRNA expression analyses by qPCR and nascent RNA capture kit revealed that STK160830 showed a decreased mRNA expression, which was similar to that induced by the RNA synthesis inhibitor actinomycin D but differed to some extent. Furthermore, unlike other RNA synthesis inhibitors such as actinomycin D, p53 accumulation by STK160830 alone was negligible, and a DNA melting-curve analysis showed very weak DNA-intercalating activity, indicating that STK160830 is a useful inhibitor for RNA synthesis without triggering p53-mediated damage responses. Full article

Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14) p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors. Full article

Objectives: This study aimed to find the optimal radiotherapy VMAT plans, that achieved high conformity and homogeneity to the planned target volume (PTV), and minimize the dose to nearby organs at risk including the non-PTV lung, heart and oesophagus for patients with centrally located non-small Cell Lung Cancer. Methods: A total of 18 patients who were treated for stage III centrally located non-small Cell Lung Cancer were selected retrospectively for this study. Identical CT datasets, 4D CT and structure dataset were used for radiotherapy planning based on single-planar VMAT (SP-VMAT), dual-planar VMAT (DP-VMAT) and Hybrid VMAT (H-VMAT). For SP-VMAT, one full arc and two half arcs were created on single-plane with couch at 0°. For DP-VMAT, one full arc was created with couch at 0°, and two half arcs with couch rotation of 330° or 30°. For H-VMAT, anterior-posterior opposing fixed beam and two half arcs were planned at couch at 0°. Dose constraints were adhered to the RTOG0617. Dose volumetric parameters were collected for statistical analysis. Results: There were no significant differences for the PTV, HI, CI between the SP-VMAT, DP-VMAT and H-VMAT. For the non-PTV lungs, Dmean, V20, V10, V5, D1500 and D1000 were significantly lower (2.05 Gy, 6.47%, 15.89%, 11.66% 4.17 Gy and 5.47 Gy respectively) in H-VMAT than that of SP-VMAT (all p < 0.001). For the oesophagus, Dmax, Dmean, V30 and V18.8 of H-VMAT were 0.08 Gy, 1.73 Gy, 5.54% and 7.17% lower than that of the SP-VMAT plan. For the heart, Dmean, V34, V28, V20 and V10 of DP-VMAT were lower than that of SP-VMAT by 1.45 Gy, 0.65%, 1.74%, 4.8% and 7.11% respectively. Conclusion: The proposed H-VMAT showed more favourable plan quality than the SP-VMAT for centrally located stage III NSCLC, in particular for non-PTV lungs and the oesophagus. It will benefit patients, especially those who planned for immunotherapy (Durvalumab) after standard chemo-irradiation. The proposed DP-VMAT plan showed significant dose reduction to the heart when compared to the H-VMAT plan. Full article

Glioblastoma is one of the most aggressive brain tumors. Given the poor prognosis of this disease, novel methods for glioblastoma treatment are needed. Virotherapy is one of the most actively developed approaches for cancer therapy today. VV-GMCSF-Lact is a recombinant vaccinia virus with deletions of the viral thymidine kinase and growth factor genes and insertions of the granulocyte–macrophage colony-stimulating factor and oncotoxic protein lactaptin genes. The virus has high cytotoxic activity against human cancer cells of various histogenesis and antitumor efficacy against breast cancer. In this work, we show VV-GMCSF-Lact to be a promising therapeutic agent for glioblastoma treatment. VV-GMCSF-Lact effectively decreases the viability of glioblastoma cells of both immortalized and patient-derived cultures in vitro, crosses the blood–brain barrier, selectively replicates into orthotopically transplanted human glioblastoma when intravenously injected, and inhibits glioblastoma xenograft and metastasis growth when injected intratumorally. Full article

The exact pathogenesis of syringomyelia is unknown. Epidural venous distention during raised intrathoracic pressure (Valsalva) may cause impulsive movement of fluid (“slosh”) within the syrinx. Such a slosh mechanism is a proposed cause of syrinx dissection into spinal cord parenchyma resulting in craniocaudal propagation of the cavity. We sought to test the “slosh” hypothesis by epidural excitation of CSF pulse in a computer model of canine syringomyelia. Our previously developed canine syringomyelia computer model was modified to include an epidural pressure pulse. Simulations were run for: cord free of cavities; cord with small syringes at different locations; and cord with a syrinx that was progressively expanding caudally. If small syringes are present, there are peaks of stress at those locations. This effect is most pronounced at the locations at which syringes initially form. When a syrinx is expanding caudally, the peak stress is typically at the caudal end of the syrinx. However, when the syrinx reaches the lumbar region; the stress becomes moderate. The findings support the “slosh” hypothesis, suggesting that small cervical syringes may propagate caudally. However, when the syrinx is large, there is less focal stress, which may explain why a syrinx can rapidly expand but then remain unchanged in shape over years. Full article

G9a is a lysine methyltransferase catalyzing the majority of histone H3 mono- and dimethylation at Lys-9 (H3K9), responsible for transcriptional repression events in euchromatin. G9a has been shown to methylate various lysine residues of non-histone proteins and acts as a coactivator for several transcription factors. This review will provide an overview of the structural features of G9a and its paralog called G9a-like protein (GLP), explore the biochemical features of G9a, and describe its post-translational modifications and the specific inhibitors available to target its catalytic activity. Aside from its role on histone substrates, the review will highlight some non-histone targets of G9a, in order gain insight into their role in specific cellular mechanisms. Indeed, G9a was largely described to be involved in embryonic development, hypoxia, and DNA repair. Finally, the involvement of G9a in cancer biology will be presented. Full article