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Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry
No full textMitosis induces cellular rearrangements like spindle formation, Golgi fragmentation, and nuclear envelope breakdown. Similar to certain retroviruses, nuclear delivery during entry of human papillomavirus (HPV) genomes is facilitated by mitosis, during which minor capsid protein L2 tethers viral DNA to mitotic chromosomes. However, the mechanism of viral genome delivery and tethering to condensed chromosomes is barely understood. It is unclear, which cellular proteins facilitate this process or how this process is regulated. This work identifies crucial phosphorylations on HPV minor capsid protein L2 occurring at mitosis onset. L2’s chromosome binding region (CBR) is sequentially phosphorylated by the master mitotic kinases CDK1 and PLK1. L2 phosphorylation, thus, regulates timely delivery of HPV vDNA to mitotic chromatin during mitosis. In summary, our work demonstrates a crucial role of mitotic kinases for nuclear delivery of viral DNA and provides important insights into the molecular mechanism of pathogen import into the nucleus during mitosis
Systematic review of candidate prognostic factors for falling in older adults identified from motion analysis of challenging walking tasks
No full textThe objective of this systematic review is to identify motion analysis parameters measured during challenging walking tasks which can predict fall risk in the older population. Numerous studies have attempted to predict fall risk from the motion analysis of standing balance or steady walking. However, most falls do not occur during steady gait but occur due to challenging centre of mass displacements or environmental hazards resulting in slipping, tripping or falls on stairs. We conducted a systematic review of motion analysis parameters during stair climbing, perturbed walking and obstacle crossing, predictive of fall risk in healthy older adults. We searched the databases of Pubmed, Scopus and IEEEexplore. A total of 78 articles were included, of which 62 simply compared a group of younger to a group of older adults. Importantly, the differences found between younger and older adults did not match those found between older adults at higher and lower risk of falls. Two prospective and six retrospective fall history studies were included. The other eight studies compared two groups of older adults with higher or lower risk based on mental or physical performance, functional decline, unsteadiness complaints or task performance. A wide range of parameters were reported, including outcomes related to success, timing, foot and step, centre of mass, force plates, dynamic stability, joints and segments. Due to the large variety in parameter assessment methods, a meta-analysis was not possible. Despite the range of parameters assessed, only a few candidate prognostic factors could be identified: older adults with a retrospective fall history demonstrated a significant larger step length variability, larger step time variability, and prolonged anticipatory postural adjustments in obstacle crossing compared to older adults without a fall history. Older adults who fell during a tripping perturbation had a larger angular momentum than those who did not fall. Lastly, in an obstacle course, reduced gait flexibility (i.e., change in stepping pattern relative to unobstructed walking) was a prognostic factor for falling in daily life. We provided recommendations for future fall risk assessment in terms of study design. In conclusion, studies comparing older to younger adults cannot be used to explore relationships between fall risk and motion analysis parameters. Even when comparing two older adult populations, it is necessary to measure fall history to identify fall risk prognostic factors
Network analysis of polymicrobial chronic wound infections in Masanga, Sierra Leone
No full textBackground: Chronic wounds are frequently colonized or infected with multiple bacterial or fungal species, which can both promote or inhibit each other. Network analyses are helpful to understand the interplay of these species in polymicrobial infections. Our aim was to analyse the network of bacterial and fungal species in chronic wounds. Methods: Swabs (n = 163) from chronic wound infections (Masanga, Sierra Leone, 2019–2020) were screened for bacterial and fungal species using non-selective agars. Some of these wounds were suspected but not confirmed Buruli ulcer. Species identification was done with MALDI-TOF mass spectrometry. Network analysis was performed to investigate co-occurrence of different species within one patient. All species with n ≥ 10 isolates were taken into account. Results: Of the 163 patients, 156 had a positive wound culture (median of three different species per patient; range 1–7). 'Pseudomonas aeruginosa' (n = 75) was the dominating species with frequent co-detections of 'Klebsiella pneumoniae' (21 cases; OR = 1.36, 95%CI: 0.63–2.96, p = 0.47), 'Staphylococcus aureus' (14 cases; OR = 1.06, 95%CI: 0.44–2.55, p = 1) and 'Proteus mirabilis' (13 cases; OR = 0.84, 95%CI: 0.35–1.99, p = 0.69). Conclusion: The culturome of chronic wounds in Sierra Leonean patients is highly diverse and characterized by the co-occurrence of 'P. aeruginosa, K. pneumoniae' and 'S. aureus'
A 5-min paradigm to evoke robust emotional reactivity in neuroimaging studies
No full textThe advent of the Research Domain Criteria (RDoC) approach to funding translational neuroscience has highlighted a need for research that includes measures across multiple task types. However, the duration of any given experiment is quite limited, particularly in neuroimaging contexts, and therefore robust estimates of multiple behavioral domains are often difficult to achieve. Here we offer a “turn-key” emotion-evoking paradigm suitable for neuroimaging experiments that demonstrates strong effect sizes across widespread cortical and subcortical structures. This short series could be easily added to existing fMRI protocols, and yield a reliable estimate of emotional reactivity to complement research in other behavioral domains. This experimental adjunct could be used to enable an initial comparison of emotional modulation with the primary behavioral focus of an investigator’s work, and potentially identify new relationships between domains of behavior that have not previously been recognized
Can a growing battery industry remain within planetary boundaries?
No full textThe rapid growth of the battery industry leads to a high demand for critical raw materials, an increasing amount of battery waste and environmental impacts along the value-chain. Several life cycle assessments have compared the relative environmental impacts of different battery technologies, production processes, or locations. However, an assessment of the environmental impacts of batteries on a planetary scale is missing. Therefore, we provide a connection between the environmental impacts of the potentially circular battery value chain and the planetary boundaries framework. Transgression of planetary boundaries will lead the Earth down an unstable path, which should be avoided. While the use of batteries in the automotive industry has significant positive impact on the environmental footprint, the battery production will clearly transgress its assigned share of the safe operating space in three planetary boundaries in 2030, 2035 and 2040 on its current trajectory. Consumption of critical raw materials accounts for most of the planetary footprint, encouraging the development of sodium-ion batteries and circular economy strategies. Alongside high recycling rates, the consequent implementation of process innovations, such as dry coating and direct lithium extraction, and the use of renewable energy will reduce the transgression of planetary boundaries. Still, further efforts are required to bring the battery industry in line with its safe operating space for phosphorous cycle and climate change. To avoid the prospect of strict policy interventions, our work encourages the fast-growing battery industry to assess innovations and demand projections through a planetary boundary lens
Comparative Evaluation of Compression Testing Methods for Murine Lumbar Vertebral Bodies: Identifying Most Reliable and Reproducible Techniques for Assessing Compressive Strength
No full textThis study evaluates four compression testing methods to determine the most reliable and reproducible technique for assessing the compression strength of murine lumbar vertebral bodies. Twenty female C57BL/6 mice (12 weeks old) were randomized into four groups: Group 1, compression of the complete lumbar vertebral body (LVB) with dorsal spinal processes; Group 2, compression at the vertebral body surface; Group 3, compression at the vertebral body surface after vertebral arch resection; Group 4, resection of the vertebral arch with straightening of the intervertebral joint surface. A mono-axial static testing machine applied compression, measuring load to failure, stiffness, yield load, and elasticity modulus. Method 1 resulted in significantly higher load-to-failure and yield-to-failure (25.9 N compared to 18.2 N, and twice 12 N for Methods 2–4), with the least variation in relative values. Method 3 had increased stiffness and a significantly higher Young’s modulus (232 N/mm, in contrast to 101, 130, and 145 N/mm for Methods 1, 2, and 4, respectively) but yielded inconsistent results. Method 4 showed the greatest variability across specimens. Method 2 yields suitable data quality as well, albeit with a slightly higher variation, and is the recommended procedure if the spinal processes have to be excluded from the measurement. Based on these findings, Method 1 produced the most consistent and reproducible data and is recommended for future studies evaluating vertebral biomechanics in mice
Establishment of a 3D co-culture model to investigate the role of primary fibroblasts in ductal carcinoma in situ of the breast
No full textBackground: Ductal carcinoma in situ (DCIS) is a precursor form of breast cancer. 13%–50% of these lesions will progress to invasive breast cancer, but the individual progression risk cannot be estimated. Therefore, all patients receive the same therapy, resulting in potential overtreatment of a large proportion of patients. Aims: The role of the tumor microenvironment (TME) and especially of fibroblasts appears to be critical in DCIS development and a better understanding of their role may aid individualized treatment. Methods and results: Primary fibroblasts isolated from benign or malignant punch biopsies of the breast and MCF10DCIS.com cells were seeded in a 3D cell culture system. The fibroblasts were cultured in a type I collagen layer beneath a Matrigel layer with MCF10DCIS.com cells. Dye-quenched (DQ) fluorescent collagen I and IV were used in collagen and Matrigel layer respectively to demonstrate proteolysis. Confocal microscopy was performed on day 2, 7, and 14 to reveal morphological changes, which could indicate the transition to an invasive phenotype. MCF10DCIS.com cells form smooth, round spheroids in co-culture with non-cancer associated fibroblasts (NAFs). Spheroids in co-culture with tumor-associated fibroblasts (TAFs) appear irregularly shaped and with an uneven surface; similar to spheroids formed from invasive cells. Therefore, these morphological changes represent the progression of an in situ to an invasive phenotype. In addition, TAFs show a higher proteolytic activity compared to NAFs. The distance between DCIS cells and fibroblasts decreases over time. Conclusion: The TAFs seem to play an important role in the progression of DCIS to invasive breast cancer. The better characterization of the TME could lead to the identification of DCIS lesions with high or low risk of progression. This could enable personalized oncological therapy, prevention of overtreatment and individualized hormone replacement therapy after DCIS
Financial Parliament
No full textEin Finanzparlament oder vergleichbares Gremium anderen Namens würde finanzielle Entscheidungen treffen oder zumindest kontrollieren für seine jeweilige Organisation, sei diese ein Staat, eine internationale Vereinigung oder ein Verein. Stimmrechte für ein Finanzparlament würden nicht nach Köpfen vergeben, sondern nach den Zahlungen an die Organisation, z. B. Steuern, Beiträge oder Spenden. Dies würde die Geldgeber stärker einbinden, könnte die Einnahmen steigern und die finanziellen Entscheidungen verbessern.A financial parliament or a similar body by another name would make or at least supervise financial decisions for its respective organisation, be it a state, an international association or a club. Voting rights for a financial parliament would not be awarded per capita, but according to payments to the organisation, e.g. taxes, contributions or donations. This would involve payers more, could increase revenue and improve financial decisions
Förderung mathematischer Grundvorstellungen durch Bewegtes Lernen:Empirische Analysen am Beispiel des Stellenwertverständnisses
No full textDie Förderung mathematischer Grundvorstellungen zählt zu den zentralen Herausforderungen des Mathematikunterrichts – besonders, wenn Lernprozesse individuell, verstehensorientiert und nachhaltig gestaltet werden sollen. Bewegtes Lernen, also die zeitliche oder inhaltliche Verbindung von Bewegung und Lernen, bietet hierbei einen innovativen Ansatz, der zunehmend in der mathematikdidaktischen Forschung diskutiert wird. Doch welches Potenzial hat dieser Zugang wirklich, insbesondere im Hinblick auf das Stellenwertverständnis, ein zentrales Fundament mathematischen Denkens? Die vorliegende Dissertation widmet sich einer umfassenden Untersuchung dieser Frage. Aufbauend auf einer interdisziplinären Analyse theoretischer Grundlagen zu Bewegung und Lernen entwickelt die Arbeit ein differenziertes Begriffsverständnis von Bewegtem Lernen im mathematischen Kontext. Als empirisches Fundament dienen Fallstudien, die im Rahmen des Lehr-Lern-Labors "MATHletics" durchgeführt wurden. Zentrale Elemente dieser Studien sind der "Zahlenteppich" als körper- und raumorientiertes Anschauungsmittel sowie bewegte Lernumgebungen, die speziell für die Förderung des Stellenwertverständnisses konzipiert wurden. Die Ergebnisse der Arbeit zeichnen ein facettenreiches Bild: Sie zeigen sowohl Potenziale als auch Grenzen Bewegten Lernens und ermöglichen konkrete Schlussfolgerungen für die Unterrichtspraxis. Dabei leistet die Dissertation nicht
nur einen bedeutenden Beitrag zur fachdidaktischen Forschung, sondern liefert auch wertvolle Impulse für die individuelle Förderung im Mathematikunterricht sowie für die Gestaltung von Studiencurricula in der Lehramtsbildung
In the Enchanted Forest of Play:Flow Consciousness and the Present Moment in Musical Improvisation with Children
No full textDie Dissertation „Im Zauberwald des Spiels: Flowbewusstsein und Gegenwartsmoment in der musikalischen Improvisation mit Kindern“ untersucht die Rolle der Musiktherapie für die seelische Entwicklung von Kindern im schulischen Kontext. Die zentrale Forschungsfrage lautet, wie musikalisches Spiel eine seelische Verwandlung ermöglicht. Der theoretische Rahmen basiert auf der morphologischen Annahme von Rosemarie Tüpker, dass musikalische Prozesse seelische Prozesse abbilden. Die vier Behandlungsschritte Leiden-Können, Methodisch-Werden, Anders-Werden und Bewerkstelligen beschreiben diese Transformation. Ziel der Arbeit ist es, den Zusammenhang zwischen Spielprozessen (Winnicott), Flow (Csikszentmihalyi), Gegenwartsmoment (Stern), Assimilation und Akkommodation (Piaget) und dem seelischen Wandel zu erörtern. In sechs Fallbeispielen wird gezeigt, wie Musiktherapie in der Schule als Raum für Selbstbildung und seelische Transformation therapeutisch genutzt werden kann.The dissertation “Im Zauberwald des Spiels: Flowbewusstsein und Gegenwartsmoment in der musikalischen Improvisation mit Kindern” examines the role of music therapy for the emotional development of children in a school context. The central research question is how musical play enables psychological transformation. The theoretical framework is based on Rosemarie Tüpker's morphological assumption that musical processes map mental processes. The four treatment steps of being able to suffer, becoming methodical, becoming different and accomplishing describe this transformation. The aim of the work is to discuss the connection between play processes (Winnicott), flow (Csikszentmihalyi), present moment (Stern), assimilation and accommodation (Piaget) and mental transformation. Six case studies show how music therapy can be used therapeutically in schools as a space for self-education and mental transformation