p53 isoforms have a high aggregation propensity, interact with chaperones and lack binding to p53 interaction partners

The p53 transcription factor family consists of the three members p53, p63, and p73. Both p63 and p73 exist in different isoforms that are well characterized. Isoforms have also been identified for p53 and it has been proposed that they are responsible for increased cancer metastasis. In contrast to the p63 and p73 isoforms, which do not contain truncations in folded domains, most of the p53 isoforms contain only parts of either the DNA-binding domain (DBD) or the oligomerization domain. To better understand the effect of p53 isoforms in cancer, we provide here a comprehensive biochemical characterization. With the exception of the Δ40p53α isoform, none of the other variants can bind to DNA with high affinity and none can upregulate transcription. Probing with antibodies, DARPins and other interaction partners confirmed that isoforms harbouring deletions in the DBD cannot interact specifically with them, but instead are bound to chaperones and other factors known to interact with misfolded proteins. Expression of isoforms with deletions in the DBD results in upregulation of cellular chaperones. If the expression level surpasses a threshold, the chaperone system can no longer keep these isoforms soluble, resulting in aggregation and co-aggregation with other factors

Classification accuracy and compatibility across devices of a new Rapid-E+ flow cytometer

The study evaluated a new model of a Plair SA airflow cytometer, Rapid-E+, and assessed its suitability for airborne pollen monitoring within operational networks. Key features of the new model are compared with the previous one, Rapid-E. A machine learning algorithm is constructed and evaluated for (i) classification of reference pollen types in laboratory conditions and (ii) monitoring in real-life field campaigns. The second goal of the study was to evaluate the device usability in forthcoming monitoring networks, which would require similarity and reproducibility of the measurement signal across devices. We employed three devices and analysed (dis-)similarities of their measurements in laboratory conditions. The lab evaluation showed similar recognition performance to that of Rapid-E, but field measurements in conditions when several pollen types were present in the air simultaneously showed notably lower agreement of Rapid-E+ with manual Hirst-type observations than those of the older model. An exception was the total-pollen measurements. Comparison across the Rapid-E+ devices revealed noticeable differences in fluorescence measurements between the three devices tested. As a result, application of the recognition algorithm trained on the data from one device to another led to large errors. The study confirmed the potential of the fluorescence measurements for discrimination between different pollen classes, but each instrument needed to be trained individually to achieve acceptable skills. The large uncertainty of fluorescence measurements and their variability between different devices need to be addressed to improve the device usability.</p

Measurement Invariance of the Meaning in Life Questionnaire Across 17 Countries

The Meaning in Life Questionnaire assesses presence of and search for meaning in life. Although the questionnaire has shown promising psychometric properties in samples from different countries, the scale’s measurement invariance across a large number of nations has yet to be assessed. This study is aimed at addressing this gap, providing insight into how meaning in life is constructed and experienced across countries and into the extent to which cross-country comparisons can be made. A total of 3867 adult participants from 17 countries, aged 30–60, balanced by gender, and with at least secondary education, completed the questionnaire as part of the Eudaimonic and Hedonic Happiness Investigation. Single sample confirmatory factor analysis, multigroup confirmatory factor analysis, and alignment optimization were applied to investigate the scale’s performance across the samples. Good psychometric properties and high levels of approximate measurement invariance emerged for the Presence subscale after removal of item 9, the only reverse-phrased item. Performance of the Search subscale varied more across samples, suggesting caution in interpreting related results supporting approximate measurement invariance. The conceptualization of presence of meaning operationalized in the corresponding subscale (without item 9) appears consistent across countries, whereas search for meaning seems to be less universally homogenous and requires further exploration. Moreover, the Meaning in Life Questionnaire does not reflect the conceptual distinction between “purpose” and “meaning” currently acknowledged by researchers. This issue should be further explored in studies addressing the scale’s performance across cultures

Family structure and functioning: Influences on adolescents psychological needs, goals and aspirations in a South African setting

This study aimed to determine the effects of family structure and functioning on basic psychological need fulfilment, life goals and aspirations of adolescents in a South African setting. Participants were 457 adolescent learners (Mage = 16.31, SD = 1.45, females = 54%, coloured = 56%) selected from four public schools in the Western Cape, South Africa. The adolescents completed the Family Assessment Device, Aspirations Index and Psychological Needs Scales. Results following multiple regression analysis suggested that a two-parent family structure predicted higher satisfaction of basic psychological needs and higher pursuit of extrinsic goals among adolescents than did a one-parent family structure. Family functioning determined pursuit of intrinsic goals by adolescents from one-parent families.DHE

Neutrino Self-Interactions: A White Paper

Neutrinos are the Standard Model (SM) particles which we understand theleast, often due to how weakly they interact with the other SM particles.Beyond this, very little is known about interactions among the neutrinos, i.e.,their self-interactions. The SM predicts neutrino self-interactions at a levelbeyond any current experimental capabilities, leaving open the possibility forbeyond-the-SM interactions across many energy scales. In this white paper, wereview the current knowledge of neutrino self-interactions from a vast array ofprobes, from cosmology, to astrophysics, to the laboratory. We also discusstheoretical motivations for such self-interactions, including neutrino massesand possible connections to dark matter. Looking forward, we discuss thecapabilities of searches in the next generation and beyond, highlighting thepossibility of future discovery of this beyond-the-SM physics.<br

Electron scattering and neutrino physics

A thorough understanding of neutrino–nucleus scattering physics is crucial for the successful execution of the entire US neutrino physics program. Neutrino–nucleus interaction constitutes one of the biggest systematic uncertainties in neutrino experiments—both at intermediate energies affecting long-baseline deep underground neutrino experiment, as well as at low energies affecting coherent scattering neutrino program—and could well be the difference between achieving or missing discovery level precision. To this end, electron–nucleus scattering experiments provide vital information to test, assess and validate different nuclear models and event generators intended to test, assess and validate different nuclear models and event generators intended to be used in neutrino experiments. Similarly, for the low-energy neutrino program revolving around the coherent elastic neutrino–nucleus scattering (CEvNS) physics at stopped pion sources, such as at ORNL, the main source of uncertainty in the evaluation of the CEvNS cross section is driven by the underlying nuclear structure, embedded in the weak form factor, of the target nucleus. To this end, parity-violating electron scattering (PVES) experiments, utilizing polarized electron beams, provide vital model-independent information in determining weak form factors. This information is vital in achieving a percent level precision needed to disentangle new physics signals from the standard model expected CEvNS rate. In this white paper, we highlight connections between electron- and neutrino–nucleus scattering physics at energies ranging from 10 s of MeV to a few GeV, review the status of ongoing and planned electron scattering experiments, identify gaps, and lay out a path forward that benefits the neutrino community. We also highlight the systemic challenges with respect to the divide between the nuclear and high-energy physics communities and funding that presents additional hurdles in mobilizing these connections to the benefit of neutrino programs

Theory of Neutrino Physics -- Snowmass TF11 (aka NF08) Topical Group Report

This is the report for the topical group Theory of Neutrino Physics (TF11/NF08) for Snowmass 2021. This report summarizes the progress in the field of theoretical neutrino physics in the past decade, the current status of the field, and the prospects for the upcoming decade.Comment: 26 pages, 5 figure

Psychometric Comparisons of Benevolent and Corrective Humor across 22 Countries: The Virtue Gap in Humor Goes International

Recently, two forms of virtue-related humor, benevolent and corrective, have been introduced. Benevolent humor treats human weaknesses and wrongdoings benevolently, while corrective humor aims at correcting and bettering them. Twelve marker items for benevolent and corrective humor (the BenCor) were developed, and it was demonstrated that they fill the gap between humor as temperament and virtue. The present study investigates responses to the BenCor from 25 samples in 22 countries (overall N = 7,226). The psychometric properties of the BenCor were found to be sufficient in most of the samples, including internal consistency, unidimensionality, and factorial validity. Importantly, benevolent and corrective humor were clearly established as two positively related, yet distinct dimensions of virtue-related humor. Metric measurement invariance was supported across the 25 samples, and scalar invariance was supported across six age groups (from 18 to 50+ years) and across gender. Comparisons of samples within and between four countries (Malaysia, Switzerland, Turkey, and the UK) showed that the item profiles were more similar within than between countries, though some evidence for regional differences was also found. This study thus supported, for the first time, the suitability of the 12 marker items of benevolent and corrective humor in different countries, enabling a cumulative cross-cultural research and eventually applications of humor aiming at the good