Functional Dissection of the Drosophila melanogaster Condensin Subunit Cap-G Reveals Its Exclusive Association with Condensin I

The heteropentameric condensin complexes have been shown to participate in mitotic chromosome condensation and to be required for unperturbed chromatid segregation in nuclear divisions. Vertebrates have two condensin complexes, condensin I and condensin II, which contain the same structural maintenance of chromosomes (SMC) subunits SMC2 and SMC4, but differ in their composition of non-SMC subunits. While a clear biochemical and functional distinction between condensin I and condensin II has been established in vertebrates, the situation in Drosophila melanogaster is less defined. Since Drosophila lacks a clear homolog for the condensin II-specific subunit Cap-G2, the condensin I subunit Cap-G has been hypothesized to be part of both complexes. In vivo microscopy revealed that a functional Cap-G-EGFP variant shows a distinct nuclear enrichment during interphase, which is reminiscent of condensin II localization in vertebrates and contrasts with the cytoplasmic enrichment observed for the other EGFP-fused condensin I subunits. However, we show that this nuclear localization is dispensable for Cap-G chromatin association, for its assembly into the condensin I complex and, importantly, for development into a viable and fertile adult animal. Immunoprecipitation analyses and complex formation studies provide evidence that Cap-G does not associate with condensin II-specific subunits, while it can be readily detected in complexes with condensin I-specific proteins in vitro and in vivo. Mass-spectrometric analyses of proteins associated with the condensin II-specific subunit Cap-H2 not only fail to identify Cap-G but also the other known condensin II-specific homolog Cap-D3. As condensin II-specific subunits are also not found associated with SMC2, our results question the existence of a soluble condensin II complex in Drosophila

University entrance qualification at vocational schools from students\u27 perspectives

Berufskollegs bieten wie Berufsfachschulen, Fachoberschulen und berufliche Gymnasien/Fachgymnasien vielfältige Möglichkeiten der berufsbezogenen Bildung. Wie diese Qualifikationsphase von jungen Erwachsenen wahrgenommen wird und welche Bedeutung das Berufskolleg für den Übergang hat, wird in diesem Beitrag anhand erster Ergebnisse einer empirischen Längsschnittstudie dokumentiert. Mittels narrativer Interviews werden nicht nur die biografische Bedeutung des Berufskollegs und die für den Übergang relevanten Entwürfe rekonstruiert, sondern auch die damit im Zusammenhang stehenden habituellen Orientierungen der jungen Erwachsenen. Eine Musterbildung zur mehrfachen Bedeutung des Berufskollegs stellt die ersten Ergebnisse der empirischen Studie zur Diskussion. (DIPF/Orig.)The Berufskolleg, the vocational school type in North Rhine-Westphalia, offers versatile opportunities of vocational education. How young adults perceive this period of qualifycation and what significance the Berufskolleg has for the transition, will be discussed in this article based on a longitudinal study. Using narrative interviews, not only the biographical significance of the Berufskolleg and the concepts, which are relevant for the process of vocational orientation, are reconstructed, but also the related habitual orientations of young adults. (DIPF/Orig.

iTReX: Interactive exploration of mono- and combination therapy dose response profiling data

High throughput screening methods, measuring the sensitivity and resistance of tumor cells to drug treatments have been rapidly evolving. Not only do these screens allow correlating response profiles to tumor genomic features for developing novel predictors of treatment response, but they can also add evidence for therapy decision making in precision oncology. Recent analysis methods developed for either assessing single agents or combination drug efficacies enable quantification of dose-response curves with restricted symmetric fit settings. Here, we introduce iTReX, a user-friendly and interactive Shiny/R application, for both the analysis of mono- and combination therapy responses. The application features an extended version of the drug sensitivity score (DSS) based on the integral of an advanced five-parameter dose-response curve model and a differential DSS for combination therapy profiling. Additionally, iTReX includes modules that visualize drug target interaction networks and support the detection of matches between top therapy hits and the sample omics features to enable the identification of druggable targets and biomarkers. iTReX enables the analysis of various quantitative drug or therapy response readouts (e.g. luminescence, fluorescence microscopy) and multiple treatment strategies (drug treatments, radiation). Using iTReX we validate a cost-effective drug combination screening approach and reveal the application’s ability to identify potential sample-specific biomarkers based on drug target interaction networks. The iTReX web application is accessible at (https://itrex.kitz-heidelberg.de).Peer reviewe

Aeroelastic Stability of Combined Plunge-Pitch Mode Shapes in a Linear Compressor Cascade †

Modern aeroengine designs strive for peak specific fuel and thermal efficiency. To achieve these goals, engines have more highly loaded compressor stages, thinner aerofoils, and blended titanium integrated disks (blisks) to reduce weight. These configurations promote the occurrence of aeroelastic phenomena such as flutter. Two important parameters known to influence flutter stability are the reduced frequency and the ratio of plunge and pitch components in a combined flap mode shape. These are used as design criteria in the engine development process. However, the limit of these criteria is not fully understood. The following research aims to bridge the gap between semi-analytical models and modern compressors by systematically investigating the flutter stability of a linear compressor cascade. This paper introduces the plunge-to-pitch incidence ratio, which is defined as a function of reduced frequency and pitch axis setback for a first flap (1F) mode shape. Using numerical simulations, in addition to experimental validation, aerodynamic damping is computed for many modes to build stability maps. The results confirm the importance of these two parameters in compressor aeroelastic stability as well as demonstrate the significance of the plunge-to-pitch incidence ratio for predicting the flutter limit

An fMRI study

Background Maternal sensitive behavior depends on recognizing one’s own child’s affective states. The present study investigated distinct and overlapping neural responses of mothers to sad and happy facial expressions of their own child (in comparison to facial expressions of an unfamiliar child). Methods We used functional MRI to measure dissociable and overlapping activation patterns in 27 healthy mothers in response to happy, neutral and sad facial expressions of their own school-aged child and a gender- and age- matched unfamiliar child. To investigate differential activation to sad compared to happy faces of one’s own child, we used interaction contrasts. During the scan, mothers had to indicate the affect of the presented face. After scanning, they were asked to rate the perceived emotional arousal and valence levels for each face using a 7-point Likert-scale (adapted SAM version). Results While viewing their own child’s sad faces, mothers showed activation in the amygdala and anterior cingulate cortex whereas happy facial expressions of the own child elicited activation in the hippocampus. Conjoint activation in response to one’s own child happy and sad expressions was found in the insula and the superior temporal gyrus. Conclusions Maternal brain activations differed depending on the child’s affective state. Sad faces of the own child activated areas commonly associated with a threat detection network, whereas happy faces activated reward related brain areas. Overlapping activation was found in empathy related networks. These distinct neural activation patterns might facilitate sensitive maternal behavior

Relationship between Borderline Personality Disorder, Emotional Availability, and Cortisol Output in Mother-Child Dyads

Background: Mothers with borderline personality disorder (BPD) often show altered emotional availability toward their own child and heightened stress vulnerability. The aims of the present study were (1) to examine total cortisol output in saliva during mother-child interaction in mothers with BPD and their children and (2) to test whether maternal nonhostility as a subscale of emotional availability mediates the relationship between maternal BPD and child total cortisol output. Methods: We investigated 16 mothers with BPD and 30 healthy control mothers (HC) and 29 children of mothers with BPD and 33 children of HC mothers. Children were between 5 and 12 years old. Salivary cortisol was collected prior to and twice after an episode of a 21-min standardized play situation between mother and child. Nonhostility was rated using the emotional availability scales. Analyses of covariance were computed to test for group differences in total cortisol output (measured with area under the curve with respect to ground). Pearson's correlation was calculated to test the association between maternal and child total cortisol output. To test the second question, a mediation analysis according to Preacher and Hayes was conducted. Results: Mothers with BPD and their children had lower total cortisol output. Maternal and child total cortisol output was significantly correlated. Contrary to our hypothesis, maternal nonhostility did not mediate the relationship between BPD and child total cortisol output. Conclusion: Results imply that the hormonal stress activity of mothers with BPD and their children is altered, which may reflect modified stress regulation and stress vulnerability in mother and child and may impact on mother-child interaction. The finding of a positive association between mother's and child total cortisol output could indicate an intergenerational transmission of these alterations

Interoperable robotics proving grounds: Investing in future-ready testing infrastructures

The increasing adoption of robots in industrial applications demands seamless communication and collaboration among a diverse range of robotic systems, a phenomenon known as interoperability. The urgency for interoperability arises from the ever-expanding use cases and innovations in robotic systems from various vendors, necessitating secure, scalable, and shareable multi-vendor interaction. However, several challenges hinder the effective implementation of interoperability, such as rapid technological changes, lack of standardisation, proprietary technologies, different levels of system autonomy, safety and security concerns, incompatibility with legacy systems, and a shortage of skilled professionals in the area. This white paper delves into the nuances of interoperability in robotics proving groundsn(also known as test beds) and offers insights into the capabilities and limitations of the current landscape. It advocates for the development of standardised testing environments, along with rigorous experimental methods and metrics. These tools are crucial for shaping regulations, attaining certifications, and effectively managing the capabilities of interoperable assets throughout their lifecycle. Assessing government initiatives' efficacy and suppliers' compliance with interoperability standards is paramount. The United Kingdom is strategically positioned to be a significant player in robotics interoperability, courtesy of its strong foothold in the energy and transport industries, such as offshore and aerospace, and an impressive network of research intensive universities and collaborative platforms. These institutions are engaged in pioneering research in areas such as modelling bio-inspired swarm systems, multi-robot coordination, sensor fusion, advanced communication, cybersecurity, and artificial intelligence. To capitalise on the UK's capabilities in robotics, the white paper recommends a multi-pronged approach. It advocates for the government to nominate experts from various sectors to participate in both national and international standardisation activities, and to establish national committees focused on robotics interoperability standards. Encouraging partnerships among government, academia, and industry is also crucial, with a focus on pre-competitive collaboration to accelerate industry growth. It is recommended to establish proving grounds and research centres for practical experimentation and development in robotics interoperability. Furthermore, the UK should actively adopt and implement international standards for robotics interoperability, particularly in government-run programmes to set a benchmark for the private sector. Alignment of national regulations with international standards is essential, along with continual updates to facilitate standard adoption. The white paper also suggests supporting pilot projects that emphasise standardisation in robotics interoperability and highlights the importance of demonstrating the benefits through case studies. Organising competitions and challenges that incentivise the development of interoperable robotic solutions based on standard protocols is encouraged. Lastly, financial backing for standardisation efforts, including sponsoring participation in standardisation committees and funding research into standards development, is deemed essential

Multiparametric MRI for Characterization of the Basal Ganglia and the Midbrain

Objectives To characterize subcortical nuclei by multi-parametric quantitative magnetic resonance imaging.Materials and Methods: The following quantitative multiparametric MR data of five healthy volunteers were acquired on a 7T MRI system: 3D gradient echo (GRE) data for the calculation of quantitative susceptibility maps (QSM), GRE sequences with and without off-resonant magnetic transfer pulse for magnetization transfer ratio (MTR) calculation, a magnetization−prepared 2 rapid acquisition gradient echo sequence for T1 mapping, and (after a coil change) a density-adapted 3D radial pulse sequence for 23Na imaging. First, all data were co-registered to the GRE data, volumes of interest (VOIs) for 21 subcortical structures were drawn manually for each volunteer, and a combined voxel-wise analysis of the four MR contrasts (QSM, MTR, T1, 23Na) in each structure was conducted to assess the quantitative, MR value-based differentiability of structures. Second, a machine learning algorithm based on random forests was trained to automatically classify the groups of multi-parametric voxel values from each VOI according to their association to one of the 21 subcortical structures.Results The analysis of the integrated multimodal visualization of quantitative MR values in each structure yielded a successful classification among nuclei of the ascending reticular activation system (ARAS), the limbic system and the extrapyramidal system, while classification among (epi-)thalamic nuclei was less successful. The machine learning-based approach facilitated quantitative MR value-based structure classification especially in the group of extrapyramidal nuclei and reached an overall accuracy of 85% regarding all selected nuclei.Conclusion Multimodal quantitative MR enabled excellent differentiation of a wide spectrum of subcortical nuclei with reasonable accuracy and may thus enable sensitive detection of disease and nucleus-specific MR-based contrast alterations in the future

MYCN mediates cysteine addiction and sensitizes neuroblastoma to ferroptosis

Aberrant expression of MYC transcription factor family members predicts poor clinical outcome in many human cancers. Oncogenic MYC profoundly alters metabolism and mediates an antioxidant response to maintain redox balance. Here we show that MYCN induces massive lipid peroxidation on depletion of cysteine, the rate-limiting amino acid for glutathione (GSH) biosynthesis, and sensitizes cells to ferroptosis, an oxidative, non-apoptotic and iron-dependent type of cell death. The high cysteine demand of MYCN-amplified childhood neuroblastoma is met by uptake and transsulfuration. When uptake is limited, cysteine usage for protein synthesis is maintained at the expense of GSH triggering ferroptosis and potentially contributing to spontaneous tumor regression in low-risk neuroblastomas. Pharmacological inhibition of both cystine uptake and transsulfuration combined with GPX4 inactivation resulted in tumor remission in an orthotopic MYCN-amplified neuroblastoma model. These findings provide a proof of concept of combining multiple ferroptosis targets as a promising therapeutic strategy for aggressive MYCN-amplified tumors