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The dynamin-related guanosine triphosphatase, Drp1 (encoded by Dnm1l), plays a central role in mitochondrial fission and is requisite for numerous cellular processes; however, its role in muscle metabolism remains unclear. Here, we show that, among human tissues, the highest number of gene correlations with DNM1L is in skeletal muscle. Knockdown of Drp1 (Drp1-KD) promoted mitochondrial hyperfusion in the muscle of male mice. Reduced fatty acid oxidation and impaired insulin action along with increased muscle succinate was observed in Drp1-KD muscle. Muscle Drp1-KD reduced complex II assembly and activity as a consequence of diminished mitochondrial translocation of succinate dehydrogenase assembly factor 2 (Sdhaf2). Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes. Drp1 is critical in maintaining mitochondrial complex II assembly, lipid oxidation, and insulin sensitivity, suggesting a mechanistic link between mitochondrial morphology and skeletal muscle metabolism, which is clinically relevant in combatting metabolic-related diseases.

Abstract Background Night shift work during pregnancy has been associated with differential DNA methylation in placental tissue, but no studies have explored this association in cord blood. We aimed to examine associations of maternal night shift work with cord blood DNA methylation. Methods A total of 4487 mother–newborn pairs from 7 studies were included. Maternal night shift work during pregnancy was ascertained via questionnaires and harmonized into “any” versus “no”. DNA methylation was measured in cord blood using the Illumina Infinium Methylation arrays. Robust linear regression models adjusted for relevant confounders were run in the individual cohorts, and results were meta-analyzed. Results Maternal night shift work during pregnancy ranged from 3.4% to 26.3%. Three CpGs were differentially methylated in relation to maternal night shift work during pregnancy at a false discovery rate adjusted P

Abstract Recent developments in mass spectrometry-based proteomics have established it as a robust tool for system-wide analyses essential for pathophysiological research. While post-mortem samples are a critical source for these studies, our understanding of how body decomposition influences the proteome remains limited. Here, we have revisited published data and conducted a clinically relevant time-course experiment in mice, revealing organ-specific proteome regulation after death, with only a fraction of these changes linked to protein autolysis. The liver and spleen exhibit significant proteomic alterations within hours post-mortem, whereas the heart displays only modest changes. Additionally, subcellular compartmentalization leads to an unexpected surge in proteome alterations at the earliest post-mortem interval (PMI). Additionally, we have conducted a comprehensive analysis of semi-tryptic peptides, revealing distinct consensus motifs for different organs, indicating organ-specific post-mortem protease activity. In conclusion, our findings emphasize the critical importance of considering PMI effects when designing proteomics studies, as these effects may significantly overshadow the impacts of diseases. Preferably, the samples should be taken in the operation room, especially for studies including subcellular compartmentalization or trans-organ comparison. In single-organ studies, the planning should involve careful control of PMI.

Abstract The proline-rich antimicrobial designer peptide Api137 inhibits protein expression in bacteria by binding simultaneously to the ribosomal polypeptide exit tunnel and the release factor (RF), depleting the cellular RF pool and leading to ribosomal arrest at stop codons. This study investigates the additional effect of Api137 on the assembly of ribosomes using an Escherichia coli reporter strain expressing one ribosomal protein per 30S and 50S subunit tagged with mCherry and EGFP, respectively. Separation of cellular extracts derived from cells exposed to Api137 in a sucrose gradient reveals elevated levels of partially assembled and not fully matured precursors of the 50S subunit (pre-50S). High-resolution structures obtained by cryogenic electron microscopy demonstrate that a large proportion of pre-50S states are missing up to five proteins (uL22, bL32, uL29, bL23, and uL16) and have misfolded helices in 23S rRNA domain IV. These data suggest a second mechanism for Api137, wherein it disrupts 50S subunit assembly by inducing the formation of misfolded precursor particles potentially incapable of evolving into active ribosomes, suggesting a bactericidal mechanism.

While ChatGPT has recently become very popular, AI has a long history and philosophy. This paper intends to explore the promises and pitfalls of the Generative Pre-trained Transformer (GPT) AI and potentially future technologies by adopting a speculative methodology. Speculative future narratives with a specific focus on educational contexts are provided in an attempt to identify emerging themes and discuss their implications for education in the 21st century. Affordances of (using) AI in Education (AIEd) and possible adverse effects are identified and discussed which emerge from the narratives. It is argued that now is the best of times to define human vs AI contribution to education because AI can accomplish more and more educational activities that used to be the prerogative of human educators. Therefore, it is imperative to rethink the respective roles of technology and human educators in education with a future-oriented mindset.

The species Chiton echinatus was first described by Barmes in 1824. Subsequently, it has been allocated to several widely distributed genera (e.g., Acanthopleura, Enoplochiton, Mesotomura) within the subfamily Acanthopleurinae. In order to resolve this species’ taxonomic uncertainty, specimens were collected throughout its entire distribution (i.e. from Peru and Chile) and subjected to a series of morphological and phylogenetic analyses. Scanning electron microscopy was used to improve this species’ morphological description, whereas publicly available sequences were used to infer its phylogenetic position. Morphological and phylogenetic analyses suggest that this species merits its own genus, endemic to the Southeastern Pacific. Of the aforementioned genera, Mesotomura appears to be the most appropriate designation. Therefore, it is proposed that the name Mesotomura echinata be restored, and the range of this species be extended to 39° S.

Background and aims: The 2019 European Society of Cardiology guidelines for the management of dyslipidemia consider the use of high-dose marine omega-3 fatty acid (FA) eicosapentaenoic acid (EPA) supplementation (icosapent ethyl 2 × 2g/day) to lower residual cardiovascular risk in high-risk patients with hypertriglyceridemia. This study aimed to assess the eligibility for omega-3 FA-EPA supplementation in patients with acute coronary syndromes (ACS). Methods: In a prospective Swiss cohort of patients hospitalized for ACS, eligibility for marine omega-3 FA-EPA, defined as plasma triglyceride levels ranging from 1.5 to 5.6 mmol/l, was assessed at baseline and one-year follow-up and compared across subgroups. Lipid-lowering therapy intensification with statin and ezetimibe was modelled to simulate a hypothetical systematic treatment and its effect on omega-3 FA-EPA supplementation eligibility. Results: Of 2643 patients, 98 % were prescribed statin therapy at discharge, including 62 % at a high-intensity regimen; 93 % maintained it after one year, including 53 % at a high-intensity regimen. The use of ezetimibe was 3 % at discharge and 7 % at one year. Eligibility was observed in 32 % (32 % men, 29 % women) one year post-ACS. After modelling systematic treatment with statins, ezetimibe, and both, eligibility decreased to 31 %, 25 % and 24 %, respectively. Eligibility was higher in individuals aged

The emergence of open educational resources (OER) represents one of the most significant educational developments in the 21st century. Given their capacity to be freely adapted, re-used, and shared in different contexts, OER expand the options for educators. This paper reports on an initial study concerning such choices in which educators' personalities are investigated in relation to the OER adoption. Choosing open approaches has been shown to correlate with personal attitudes and several studies have highlighted the potential and need for investigating how personality might affect OER adoption. To address this gap, this study investigates the impact of educators' personality differences in relation to OER adoption. The analysis focuses specifically on the perception towards OER and the intention to use OER using the Five-Factor Model (FFM) to identify educators' personalities. Following a mixed methods approach, data collected from university educators using questionnaires (57 respondents) and interviews (15 respondents) are discussed in a two-stage hierarchical regression analysis. Demographic variables (age and gender) do not show any significant relationship. Findings reveal that while the explored five personality dimensions do not have an impact on the educator attitudes towards OER, they seem to have a significant impact on their intention to use OER. Specifically, only three personality dimensions -- namely, extraversion, agreeableness, and openness -- have a significant impact on the intention to use OER. This shows that 'open attitude' (mixing extraversion, and agreeableness, and openness) may be a fundamental prerequisite for educators to engage in open teaching practices, including the use of OER.

In terms of scale, shock, and disenfranchisement, the disruption to formal education arising from COVID-19 has been unprecedented. Anecdotally, responses from teachers and educators around the world range from heightened caution to being inspired by distance education as the "new normal." Of all the challenges, face-to-face and formal teaching have been most heavily affected. Despite some education systems demonstrating resilience, a major challenge is sustaining quality and inclusiveness in formal education suddenly delivered at a distance. In probing these issues, this article profiles international perspectives on the role of open education in responding to the impact on formal school and higher education caused by the COVID-19 pandemic. We proceed by highlighting and analysing practices and case studies from 13 countries representing all global regions, identifying and discussing the challenges and opportunities that have presented themselves. Reports cover the period from the beginning of 2020 until 11 March 2021, the first anniversary of the COVID-19 outbreak as declared by the World Health Organization. In our comparative study, we identify seven key aspects of which three (missing infrastructure and sharing OER, open education and access to OER, and urgent need for professional development and training for teachers) are directly related to open education at a distance. After comparing examples of existing practice, we make recommendations and offer insights into how open education strategies can lead to interventions that are effective and innovative--to improve formal education at a distance in schools and universities in the future.

Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or cord blood (n = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P-value

A modern area of research in cancer treatment is magnetic drug targeting (MDT) with superparamagnetic iron oxide nanoparticles (SPIONs). In order to understand the processes involved in MDT in more detail and to be able to perform this therapy as efficiently as possible, a monitoring system for the spatial distribution of SPIONs in biological tissue is required. One approach is to use magnetomotive ultrasound (MMUS) to monitor the spatial distribution over time. However, the spatial distribution of SPIONs cannot be quantitatively determined applying basic MMUS algorithms. Therefore, MMUS has been extended by a simulation part to quantitatively determine the spatial distribution of SPIONs. This extended MMUS algorithm requires the material parameters and the geometry of the target tumorous tissue. In this contribution, we describe an ultrasound-based eigenfrequency analysis combined with an iterative inverse simulation-based method to determine the mechanical parameter Young's modulus of tissue mimicking phantoms. The presented approach yields a good estimate of the Young's modulus compared to the result from a compression test.