Search

Soft skills enable the individual to successfully face the problems and challenges of a complex society in flux and under constant uncertainty. Music, in its different forms of expression, is here introduced as an ideal tool for the development of intrapersonal and action skills such as adaptability, optimism and proactivity. In this paper we analyse a case study regarding a project carried out by and for future teachers. Our data collection methods included questionnaires, observations, student productions and interviews. The results reveal that music can be a mediating element for the development of soft skills. Specifically, it has been observed that music can help the individual to face and effectively resolve changing and novel situations that require self-efficacy, self-confidence and social support. Music can also improve the physical and socio-emotional well-being of individuals as well as helping them successfully face adversity.

Abstract Dysregulated mitochondrial fusion and fission has been implicated in the pathogenesis of numerous diseases. We have identified a novel function of the p53 family protein TAp73 in regulating mitochondrial dynamics. TAp73 regulates the expression of Optic Atrophy 1 (OPA1), a protein responsible for controlling mitochondrial fusion, cristae biogenesis and electron transport chain function. Disruption of this axis results in a fragmented mitochondrial network and an impaired capacity for energy production via oxidative phosphorylation. Owing to the role of OPA1 in modulating cytochrome c release, TAp73−/− cells display an increased sensitivity to apoptotic cell death, e.g., via BH3-mimetics. We additionally show that the TAp73/OPA1 axis has functional relevance in the upper airway, where TAp73 expression is essential for multiciliated cell differentiation and function. Consistently, ciliated epithelial cells of Trp73 −/− (global p73 knock-out) mice display decreased expression of OPA1 and perturbations of the mitochondrial network, which may drive multiciliated cell loss. In support of this, Trp73 and OPA1 gene expression is decreased in chronic obstructive pulmonary disease (COPD) patients, a disease characterised by alterations in mitochondrial dynamics. We therefore highlight a potential mechanism involving the loss of p73 in COPD pathogenesis. Our findings also add to the growing body of evidence for growth-promoting roles of TAp73 isoforms.

Abstract Vaccination reduces morbidity and mortality due to infections, but efficacy may be limited due to distinct immunogenicity at the extremes of age. This raises the possibility of employing adjuvants to enhance immunogenicity and protection. Early IFNγ production is a hallmark of effective vaccine immunogenicity in adults serving as a biomarker that may predict effective adjuvanticity. We utilized mass cytometry (CyTOF) to dissect the source of adjuvant-induced cytokine production in human blood mononuclear cells (BMCs) from newborns (~39-week-gestation), adults (~18-63 years old) and elders (>65 years of age) after stimulation with pattern recognition receptors agonist (PRRa) adjuvants. Dimensionality reduction analysis of CyTOF data mapped the BMC compartment, elucidated age-specific immune responses and profiled PRR-mediated activation of monocytes and DCs upon adjuvant stimulation. Furthermore, we demonstrated PRRa adjuvants mediated innate IFNγ induction and mapped NK cells as the key source of TLR7/8 agonist (TLR7/8a) specific innate IFNγ responses. Hierarchical clustering analysis revealed age and TLR7/8a-specific accumulation of innate IFNγ producing γδ T cells. Our study demonstrates the application of mass cytometry and cutting-edge computational approaches to characterize immune responses across immunologically distinct age groups and may inform identification of the bespoke adjuvantation systems tailored to enhance immunity in distinct vulnerable populations.

Abstract Background The “Virtual Semester for Medical Research Aachen” (vSEMERA) is an international, interdisciplinary, virtual education program developed for health profession students. The first edition (2021) was hosted by the Medical Faculty of RWTH Aachen University (Germany) in cooperation with Centro Universitário Christus (Brazil) and Universidad Peruana Cayetano Heredia (Peru). The primary aim of the 12-weeks program was to provide students with skills in health science research and prepare them for scientific career paths. Methods vSEMERA was built on a virtual learning platform, the “vSEMERA-Campus”, designed to foster students’ learning process and social interactions. Maximum flexibility was offered through synchronous and asynchronous teaching, enabling participants to join via any device from any part of the Globe alongside their regular studies. For the program’s first edition (September - November 2021), health profession students from Germany, Brazil, Peru, Spain, and Italy filled all 30 available spots. Satisfaction, quality of the program and courses offered, as well as perceived learning outcomes, were examined using questionnaires throughout and at the end of the program. Results The program received a rating of 4.38 out of 5 stars. While it met most expectations (4.29 out of 5), participants were unable to attend as many courses as intended (2.81 out of 5), mainly due to scheduling conflicts with the home university schedule (46%), internships (23%), and general timing issues (31%). Participants acknowledged considerable improvements in their scientific skills, English language skills, confidence in scientific project management, research career progression, and enthusiasm for a scientific career. Conclusions vSEMERA represents a promising example of an online international learning and exchange program using pedagogical and technological elements of virtual collaboration and teaching. In addition to advancing future vSEMERA editions, our results may offer insights for similar projects that address the targeted integration of scientific research education into an international, digital learning environment.

We studied the impact of Ba2+ ions on the function and structure of large conductance potassium (BK) channels. Ion composition has played a crucial role in the physiological studies of BK channels due to their ability to couple ion composition and membrane voltage signaling. Unlike Ca2+, which activates BK channels through all Regulator of K+Conductance (RCK) domains, Ba2+ has been described as specifically interacting with the RCK2 domain. It has been shown that Ba2+ also blocks potassium permeation by binding to the channel’s selectivity filter. The Cryo-EM structure of the Aplysia BK channel in the presence of high concentration Ba2+ here presented (PDBID: 7RJT) revealed that Ba2+ occupies the K+ S3 site in the selectivity filter. Densities attributed to K+ ions were observed at sites S2 and S4. Ba2+ ions were also found bound to the high-affinity Ca2+ binding sites RCK1 and RCK2, which agrees with functional work suggesting that the Ba2+ increases open probability through the Ca2+ bowl site (RCK2). A comparative analysis with a second structure here presented (PDBID: 7RK6), obtained without additional Ba2+, shows localized changes between the RCK1 and RCK2 domains, suggestive of coordinated dynamics between the RCK ion binding sites with possible relevance for the activation/blockade of the channel. The observed densities attributed to Ba2+ at RCK1 and RCK2 sites and the selectivity filter contribute to a deeper understanding of the structural basis for Ba2+'s dual role in BK channel modulation, adding to the existing knowledge in this field.

Maternally-loaded factors in the egg accumulate during oogenesis and are essential for the acquisition of oocyte and egg developmental competence to ensure the production of viable embryos. However, their molecular nature and functional importance remain poorly understood. Here, we present a collection of 9 recessive maternal-effect mutants identified in a zebrafish forward genetic screen that reveal unique molecular insights into the mechanisms controlling the vertebrate oocyte-to-embryo transition. Four genes, over easy, p33bjta, poached and black caviar, were found to control initial steps in yolk globule sizing and protein cleavage during oocyte maturation that act independently of nuclear maturation. The krang, kazukuram, p28tabj, and spotty genes play distinct roles in egg activation, including cortical granule biology, cytoplasmic segregation, the regulation of microtubule organizing center assembly and microtubule nucleation, and establishing the basic body plan. Furthermore, we cloned two of the mutant genes, identifying the over easy gene as a subunit of the Adaptor Protein complex 5, Ap5m1, which implicates it in regulating intracellular trafficking and yolk vesicle formation. The novel maternal protein Krang/Kiaa0513, highly conserved in metazoans, was discovered and linked to the function of cortical granules during egg activation. These mutant genes represent novel genetic entry points to decipher the molecular mechanisms functioning in the oocyte-to-embryo transition, fertility, and human disease. Additionally, our genetic adult screen not only contributes to the existing knowledge in the field but also sets the basis for future investigations. Thus, the identified maternal genes represent key players in the coordination and execution of events prior to fertilization.

Abstract Self‐reflection practice in coaching can help with time management by promoting self‐awareness. Through this process, a coach can identify habits, tendencies and behaviours that may be causing distraction or make them less productive. This insight can be used to make changes in behaviour and establish new habits that promote effective use of time. This can also help the coach to prioritise goals and create a clear roadmap. An AI powered system has been proposed that maps the conversion onto topics and relations that could help the coach with note‐taking and progress identification throughout the session. This system enables the coach to actively self‐reflect on time management and make sure the conversation follows the target framework. This will help the coach to better understand the goal setting, breakthrough moment, and client accountability. The proposed end‐to‐end system is capable of identifying coaching segments (Goal, Option, Reality, and Way forward) across a session with 85% accuracy. Experimental evaluation has also been conducted on the coaching dataset which includes over 1k one‐to‐one English coaching sessions. In regards to the novelty, there are no datasets of such nor study of this kind to enable self‐reflection actively and evaluate in‐session performance of the coach.

Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4-36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. We found 120 occurrences of probably damaging variants (116 heterozygous; four homozygous) among 45 of 104 recognized HDL candidate genes. Those with the highest prevalence of damaging variants were ABCA1 (n = 20), STAB1 (n = 9), OSBPL1A (n = 8), CPS1 (n = 8), CD36 (n = 7), LRP1 (n = 6), ABCA8 (n = 6), GOT2 (n = 5), AMPD3 (n = 5), WWOX (n = 4), and IRS1 (n = 4). Binomial analysis for damaging missense or loss-of-function variants identified the ABCA1 and LDLR genes at genome-wide significance. In conclusion, whole-exome sequencing of individuals with low HDL-C showed the burden of damaging rare variants in the ABCA1 and LDLR genes is particularly high and revealed numerous occurrences in HDL candidate genes, including many genes identified in genome-wide association study reports. Many of these genes are involved in cancer biology, which accords with epidemiologic findings of the association of HDL deficiency with increased risk of cancer, thus presenting a new area of interest in HDL genomics.

Determining the axial length (AL) of the eye is of significant interest in the management of myopia. However, the devices that allow this value to be obtained are either expensive, for example, optical biometers, or inconvenient for use in pediatric population, such is the case with ultrasound biometers. Therefore, this study aimed to develop a mathematical model for estimating the AL value based on easily obtainable variables, with the novel addition of body height to the analysis. A total of 170 eyes of 85 myopic volunteers (mean age of 10.8 ± 1.45 years, ranging from 7 to 14 years) were included in the analysis. Participants underwent anamnesis, keratometry by NVISION-K 5001, subjective refraction by an optometrist, AL measurement by the Topcon MYAH biometer, and body height measurement. Spearman’s correlation test was employed to analyze the relationships between AL and keratometry, spherical equivalent, body height (Sperman’s correlation, all r ≥ 0.267, all p < 0.001), and age (Spearman’s correlation, p = 0.081). Subsequently, multiple regression analysis was conducted on the variables that demonstrated a previous correlation. The mathematical model obtained permits the estimation of AL based on average keratometry, spherical equivalent, and body height. This model is significant (p < 0.001) and explains 82.4% of AL variability.

Summary: Post-transcriptional mRNA regulation shapes gene expression, yet how cis-elements and mRNA translation interface to regulate mRNA stability is poorly understood. We find that the strength of translation initiation, upstream open reading frame (uORF) content, codon optimality, AU-rich elements, microRNA binding sites, and open reading frame (ORF) length function combinatorially to regulate mRNA stability. Machine-learning analysis identifies ORF length as the most important conserved feature regulating mRNA decay. We find that Upf1 binds poorly translated and untranslated ORFs, which are associated with a higher decay rate, including mRNAs with uORFs and those with exposed ORFs after stop codons. Our study emphasizes Upf1’s converging role in surveilling mRNAs with exposed ORFs that are poorly translated, such as mRNAs with long ORFs, ORF-like 3′ UTRs, and mRNAs containing uORFs. We propose that Upf1 regulation of poorly/untranslated ORFs provides a unifying mechanism of surveillance in regulating mRNA stability and homeostasis in an exon-junction complex (EJC)-independent nonsense-mediated decay (NMD) pathway that we term ORF-mediated decay (OMD).

The present study aimed to assess the symptomatic status of Convergence Insufficiency (CI) in university students from 2018 to 2023 considering the educational environment pre- and post-COVID-19 pandemic confinements. A Convergence Insufficiency Symptom Survey (CISS) was conducted annually from 2018 to 2023, excluding 2020, in an initial group of 217 third-year Optics and Optometry degree university student participants. In the final group (178 participants), the statistical differences in CISS scores between years were analysed, both overall and by questionnaire subgroup, along with associations between CISS diagnostic categories before and after 2020. Significant differences were found between years in the subscale and total score analyses (Kruskal–Wallis, both p ≤ 0.049). Pairwise comparisons showed significant differences for the performance subgroup in 2021 vs. 2019 and 2018 (Mann–Whitney, both p ≤ 0.004), while in terms of the total score, there was a statistical difference in 2021 vs. 2018 (Mann–Whitney, p < 0.001). The distribution analysis indicated a significant difference between groups (Chi, p = 0.004), with participants from 2021 or later more likely to exhibit higher CISS scores (OR = 3.47, 95%CI 1.04–8.58). The present study shows significant temporal increments in symptomatic status related to CI among university students from 2018 to 2023, indicating a potential impact of the COVID-19 pandemic educational landscape on these outcomes.