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Background: Microbial biofilms, as a hallmark of cystic fibrosis (CF) lung disease and other chronic infections, remain a desirable target for antimicrobial therapy. These biopolymer-based viscoelastic structures protect pathogenic organisms from immune responses and antibiotics. Consequently, treatments directed at disrupting biofilms represent a promising strategy for combating biofilm-associated infections. In CF patients, the viscoelasticity of biofilms is determined mainly by their polymicrobial nature and species-specific traits, such as Pseudomonas aeruginosa filamentous (Pf) bacteriophages. Therefore, we examined the impact of microbicidal ceragenins (CSAs) supported by mucolytic agents-DNase I and poly-aspartic acid (pASP), on the viability and viscoelasticity of mono- and bispecies biofilms formed by Pf-positive and Pf-negative P. aeruginosa strains co-cultured with Staphylococcus aureus or Candida albicans., Methods: The in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms' viscoelastic properties characterized by shear storage (G') and loss moduli (G"), were analyzed with a rotational rheometer., Results: Our results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters., Conclusion: Due to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents., Competing Interests: Paul B. Savage and Robert Bucki are the paid consultants to N8 Medical, which focuses on commercialization of medical devices that incorporate ceragenins. The funder provided support in the form of salaries for authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Wnorowska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This is the first study focused on Eocene dipterans of the tribe Pseudochironomini (subfamily Chironominae, family Chironomidae), based on unique materials from Baltic amber. Two new genera and three new species: Eomicromimus gen. nov. with Eomicromimus polliciformis sp. nov. and Eomicromimus serpens sp. nov., and Eoriethia gen. nov. with Eoriethia ursipes sp. nov. are presented. The systematic position of the new taxa is discussed, and an amended key to the identification of adult males of extinct and extant Pseudochironomini genera is provided. The presented analysis of the morphology of the tribe's fossil members allowed us to verify the concepts regarding the origin/homology of male diagnostic structures crucial in defining new taxa, their phylogeny, and to consolidate the terminology used in chironomid research. A new habitual name for Chironomidae, "mime midges", is also proposed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zakrzewska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Odors are important disease cues, and disgust sensitivity to body odors reflects individual differences in disease avoidance. The body odor disgust sensitivity (BODS) scale provides a rapid and valid assessment of individual differences. Nevertheless, little is known about how individual differences in BODS might correlate with overall odor perception or how it is related to other differences in emotional reactivity (e.g., affect intensity). We investigated how BODS relates to perceptual ratings of pleasant and unpleasant odors. We aggregated data from 4 experiments (total N = 190) that were conducted in our laboratory, and where valence and intensity ratings were collected. Unpleasant odors were body-like (e.g., sweat-like valeric acid), which may provide disease cues. The pleasant odors were, in contrast, often found in soap and cleaning products (e.g., lilac, lemon). Across experiments, we show that individuals with higher BODS levels perceived smells as more highly valenced overall: unpleasant smells were rated as more unpleasant, and pleasant smells were rated as more pleasant. These results suggest that body odor disgust sensitivity is associated with a broader pattern of affect intensity which causes stronger emotional responses to both negative and positive odors. In contrast, BODS levels were not associated with odor intensity perception. Furthermore, disgust sensitivity to odors coming from external sources (e.g., someone else's sweat) was the best predictor of odor valence ratings. The effects were modest in size. The results validate the BODS scale as it is explicitly associated with experimental ratings of odor valence., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zakrzewska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The study evaluates the impact of biopsychosocial factors involved in food allergy (FA) on the prevalence of eating disorders (ED). For the 5-year follow-up studies, 75 participants (aged 1-14 years) with early-onset FA and 81 healthy peers were included., Method: Participants were diagnosed with FA using antibody/cytokine content immunoassay tests. Medical history, including BMI z-scores, was completed using data obtained in response to a validated allergic questionnaire that incorporated the SCOFF and EAT-8 screening questionnaires for ED. FA was confirmed if total IgE was elevated, specific sIgE to food allergens exceeded 0.7 kUA/L and if manifestations were observed. Screening for ED was considered positive if two or more SCOFF and EAT-8 items were confirmed., Results: In the FA+ group, 50% of female participants and 6.7% of their healthy female peers reported ED. An ED+ result was more frequent in FA+ individuals than in their healthy peers (p = 0.046) although the association is weak. In the FA+/ED+ group, 25.3% of the participants were underweight, and 14.7% were overweight compared to their peers where this reached respectively 4.2% and 2.8% (p<0.005). 74% of the FA+/ED+ individuals reported elimination diet implementation and only 15% declared it was medically consulted. The prevalence of ED in the FA+ male group was consistently correlated with lack of confidence in FA issues (r = 0.5424) and in the FA+ female group with applied medical procedures (r = 0.7069; p<0.005)., Conclusion: These findings suggest that participants with FA especially struggling with lack of confidence in FA issues and those following an uncontrolled, restrictive elimination diet are more prone to food aversion and ED than their healthy peers. Applied procedures are necessary, and their neglect is associated with FA deterioration; however, the possibility of ED and biopsychosocial implications development should not be underestimated., Competing Interests: The authors have declared that no competing interests exist.

Background: Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures. This limits surgical resection and poses a considerable clinical problem. Moreover, there are no appropriate outcome prognostic factors besides the extent of surgical resection. Despite definition of molecular subgroups, the majority of childhood ependymomas present a balanced genome, which makes it difficult to establish molecular prognostic factors., Methods: The purpose of our study was to explore whether miRNA expression could be used as prognostic markers in pediatric infratentorial ependymomas. We also performed a mRNA expression pattern analysis of NELL2 and LAMA2 genes, with immunohistochemical illustrations of representative cases. The miRNA and mRNA expression was measured in 53 pediatric infratentorial ependymomas using a real-time quantitative PCR., Results: Three miRNAs were shown to efficiently differentiate between grade II and III ependymomas: miR-17-5p, miR-19a-3p, and miR-106b-5p. Survival analysis showed that the probabilities of overall (p = 0.036) and event-free survival (p = 0.002) were reduced with higher than median miRNA expression levels of miR-17-5p. Using multivariate analysis adjusted for patient's age, sex, tumor grade and localization, we showed statistically significant associations with event-free survival (p = 0004) and borderline statistical significance with overall survival (p = 0.057) for miR-17-5p. Correlation analysis of miR-19a, miR-17-5p, miR-106b revealed that their expression levels were significantly correlated with EZH2 expression, suggested marker of PFA ependymomas. Furthermore, lower expression level of LAMA2 mRNA was shown to be associated with an increased risk of death in covariate-adjusted analyses., Conclusions: Our data provide a better understanding of pediatric ependymoma and suggests the presence of plausible molecular biomarkers connected with the outcome.

Extracellular fibroblast growth factor 1 (FGF1) acts through cell surface tyrosine kinase receptors, but FGF1 can also act directly in the cell nucleus, as a result of nuclear import of endogenously produced, non-secreted FGF1 or by transport of extracellular FGF1 via endosomes and cytosol into the nucleus. In the nucleus, FGF1 can be phosphorylated by protein kinase C δ (PKCδ), and this event induces nuclear export of FGF1. To identify intracellular targets of FGF1 we performed affinity pull-down assays and identified nucleolin, a nuclear multifunctional protein, as an interaction partner of FGF1. We confirmed a direct nucleolin-FGF1 interaction by surface plasmon resonance and identified residues of FGF1 involved in the binding to be located within the heparin binding site. To assess the biological role of the nucleolin-FGF1 interaction, we studied the intracellular trafficking of FGF1. In nucleolin depleted cells, exogenous FGF1 was endocytosed and translocated to the cytosol and nucleus, but FGF1 was not phosphorylated by PKCδ or exported from the nucleus. Using FGF1 mutants with reduced binding to nucleolin and a FGF1-phosphomimetic mutant, we showed that the nucleolin-FGF1 interaction is critical for the intranuclear phosphorylation of FGF1 by PKCδ and thereby the regulation of nuclear export of FGF1.

Endocytosis of tyrosine kinase receptors can influence both the duration and the specificity of the signal emitted. We have investigated the mechanisms of internalization of fibroblast growth factor receptor 3 (FGFR3) and compared it to that of FGFR1 which is internalized predominantly through clathrin-mediated endocytosis. Interestingly, we observed that FGFR3 was internalized at a slower rate than FGFR1 indicating that it may use a different endocytic mechanism than FGFR1. Indeed, after depletion of cells for clathrin, internalization of FGFR3 was only partly inhibited while endocytosis of FGFR1 was almost completely abolished. Similarly, expression of dominant negative mutants of dynamin resulted in partial inhibition of the endocytosis of FGFR3 whereas internalization of FGFR1 was blocked. Interfering with proposed regulators of clathrin-independent endocytosis such as Arf6, flotillin 1 and 2 and Cdc42 did not affect the endocytosis of FGFR1 or FGFR3. Furthermore, depletion of clathrin decreased the degradation of FGFR1 resulting in sustained signalling. In the case of FGFR3, both the degradation and the signalling were only slightly affected by clathrin depletion. The data indicate that clathrin-mediated endocytosis is required for efficient internalization and downregulation of FGFR1 while FGFR3, however, is internalized by both clathrin-dependent and clathrin-independent mechanisms.