A collagen cell carrier seeded with autologous urothelial cells for reconstructive surgery of the urethra

Tissue Engineering (TE) ist ein neuer therapeutischer Ansatz, um dem Mangel an Spenderorganen oder -geweben gerecht zu werden. Er zielt darauf ab, Ersatzorgane herzustellen, um die Organfunktion des Empfängers zu verbessern oder zu ersetzen. Die drei Grundprinzipien des TE beinhalten die Nutzung von: 1) isolierten Zellen oder Zellersatz, 2) Signalmolekülen wie Wachstumsfaktoren, die die Zellproliferation fördern und 3) Matrices, das heißt natürlichen oder synthetischen Trägermaterialien. Durch die Nutzung von Biomaterialien als Trägermaterial können autologe zellbasierte Transplantate stabilisiert werden und damit ein strapazierfähiges künstliches Organ in vitro hergestellt werden. Mit dieser Untersuchung sollte die Tauglichkeit eines zellbesiedelten kollagenbasierten Gerüsts (collagen cell carrier - CCC) geprüft werden, Harnröhrenläsionen insbesondere Harnröhrenstrikturen als innovatives Therapiekonzept zu beheben. Dazu wurde die Viabilität und Proliferation humaner und porciner Urothelzellen ebenso wie deren Adhärenz auf dem neuen Zellträger untersucht. In vivo wurde die Biokompatibilität durch ektopische Transplantation im Nacktrattenmodell getestet und abschließend wurden zellbesiedelte Kollagenmatrices nach Induktion einer Harnröhrenstriktur in die Harnröhre von Minipigs eingesetzt. Sowohl die in vitro als auch die in vivo Daten belegten die exzellente Tauglichkeit von CCC als Trägermatrix zur Konstruktion artifizieller autologer Urotheltransplantate. Wurde eine große Anzahl an Zellen verwendet, so waren die metabolische Aktivität und Proliferation als auch die Adhärenz auf CCC vergleichbar mit der bei Aussaat auf Plastik. Das Nacktrattenmodell und das Minipigmodell wiesen die Biokompatibilität, die Integration und die Degradation der Zell-Matrix-Konstrukte in vivo nach. Damit sind die Ergebnisse dieser Studie von größter Bedeutung für die zukünftigen Therapiemöglichkeiten von Harnröhrenstrikturen und legen den Grundstein für die potentielle klinische Anwendung.Tissue engineering (TE) is a new therapeutic approach to cope with the lack of donor organs or tissues. It aims to create organ substitutes to improve the function of the recipient’s organ or to replace it. The three basic principles of TE comprise the use of: 1) isolated cells or cell substitutes, 2) signal molecules that promote cell proliferation such as growth factors and 3) matrices i.e. natural or synthetic scaffolds. Using biomaterials as scaffolds, autologous cell-based transplants can be stabilised and consequently, a solid artificial organ can be constructed in vitro. This investigation was supposed to verify the suitability of a cell seeded collagen based scaffold (collagen cell carrier - CCC) to repair urethral lesions especially urethral strictures as an innovative therapeutic concept. Therefore, viability and proliferation of human and porcine urothelial cells as well as their adherence on the new cell carrier were examined. In vivo biocompatibility was tested by ectopic transplantation in nude rats and finally, cell seeded collagen matrices were applied in minipigs’ urethras after induction of a urethral stricture. In vitro as well as in vivo investigations proved the excellent suitability of CCC as a cell carrier to create artificial autologous urothelial transplants. Metabolic activity and proliferation of urothelial cells as well as their adherence on CCC were comparable to plastic seeding when high numbers of cells were used. The nude rat model and the minipig model proved the biocompatibility, integration, and degradation of the cell matrix constructs in vivo. Hence the results of this study are of greatest value for future therapeutic options for urethral strictures and lay the foundations for potential clinical application

Energy and system size dependence of \phi meson production in Cu+Cu and Au+Au collisions

We study the beam-energy and system-size dependence of \phi meson production (using the hadronic decay mode \phi -- K+K-) by comparing the new results from Cu+Cu collisions and previously reported Au+Au collisions at \sqrt{s_NN} = 62.4 and 200 GeV measured in the STAR experiment at RHIC. Data presented are from mid-rapidity (|y|<0.5) for 0.4 < pT < 5 GeV/c. At a given beam energy, the transverse momentum distributions for \phi mesons are observed to be similar in yield and shape for Cu+Cu and Au+Au colliding systems with similar average numbers of participating nucleons. The \phi meson yields in nucleus-nucleus collisions, normalised by the average number of participating nucleons, are found to be enhanced relative to those from p+p collisions with a different trend compared to strange baryons. The enhancement for \phi mesons is observed to be higher at \sqrt{s_NN} = 200 GeV compared to 62.4 GeV. These observations for the produced \phi(s\bar{s}) mesons clearly suggest that, at these collision energies, the source of enhancement of strange hadrons is related to the formation of a dense partonic medium in high energy nucleus-nucleus collisions and cannot be alone due to canonical suppression of their production in smaller systems.Comment: 20 pages and 5 figure

Responsible Research is also concerned with generalizability: Recognizing efforts to reflect upon and increase generalizability in hiring and promotion decisions in psychology

We concur with the authors of the two target articles that Open Science practices can help combat the ongoing reproducibility and replicability crisis in psychological science and should hence be acknowledged as responsible research practices in hiring and promotion decisions. However, we emphasize that another crisis is equally threatening the credibility of psychological science in Germany: The sampling or generalizability crisis. We suggest that scientists’ efforts to contextualize their research, reflect upon, and increase its generalizability should be incentivized as responsible research practices in hiring and promotion decisions. To that end, we present concrete suggestions for how efforts to combat the additional generalizability crisis could be operationalized within Gärtner et al. (2022) evaluation scheme. Tackling the replicability and the generalizability crises in tandem will advance the credibility and quality of psychological science and teaching in Germany

IRF4 deficiency vulnerates B-cell progeny for leukemogenesis via somatically acquired Jak3 mutations conferring IL-7 hypersensitivity

The processes leading from disturbed B-cell development to adult B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) remain poorly understood. Here, we describe Irf4 −/− mice as prone to developing BCP-ALL with age. Irf4 −/− preB-I cells exhibited impaired differentiation but enhanced proliferation in response to IL-7, along with reduced retention in the IL-7 providing bone marrow niche due to decreased CXCL12 responsiveness. Thus selected, preB-I cells acquired Jak3 mutations, probably following irregular AID activity, resulting in malignant transformation. We demonstrate heightened IL-7 sensitivity due to Jak3 mutants, devise a model to explain it, and describe structural and functional similarities to Jak2 mutations often occurring in human Ph-like ALL. Finally, targeting JAK signaling with Ruxolitinib in vivo prolonged survival of mice bearing established Irf4 −/− leukemia. Intriguingly, organ infiltration including leukemic meningeosis was selectively reduced without affecting blood blast counts. In this work, we present spontaneous leukemogenesis following IRF4 deficiency with potential implications for high-risk BCP-ALL in adult humans.Deutsche Krebshilfe (German Cancer Aid) https://doi.org/10.13039/501100005972Deutsche Forschungsgemeinschaft (German Research Foundation) https://doi.org/10.13039/50110000165

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Growing into Parenting together: Similarities and Differences in Parenting Practices among First-time Parents

Numerous studies have shown the importance of coparenting in promoting healthy child development. It is assumed that a high degree of agreement on parental attitudes, behaviors and goals is conducive to successful coparenting. In the present study, we aim to expand on the current literature by investigating factors which contribute to similarities and differences in parenting behavior between mothers and fathers within the same family. Furthermore, we are examining how accurately parents perceive and assess their partner in terms of their parenting practices. Since June 2022, we are recruiting Swiss-German first-time parents that live together and have an only child at 12, 24 or 36 months (+/- 3 months). Parents are completing an online survey on parenting practices both as a self-assessment and an assessment of their partner’s parenting practices. In addition, demographic variables such as education levels, age, etc., as well as relationship satisfaction are assessed. Data collection will be continued until aimed sample size of 180 parent couples has been reached. We expect data collection to be completed in September 2022. We will run an APIM model for all four scales on parenting practices (positive parenting, responsible parenting, authoritarian parenting, inconsistent discipline) and conduct multigroup APIM analyses. We expect higher levels of parenting agreement among couples who share similar demographic backgrounds, have longer-lasting and more satisfying relationships, and among parents with younger children at 12 months in comparison to older children. Once data analysis is complete, the results will be interpreted and discussed

Does amusement broaden the thought-action repertoire of 5- and 6-year-old children?

The broaden-and-build theory introduced by Fredrickson (2001) hypothesises that positive emotions broaden an individual’s momentary thought-action repertoire, promoting them to pursue a wider range of thoughts and actions than typical. For example, the positive emotion of amusement is thought to spark the urge to “share joviality and laugh” (Fredrickson, 2013, p. 5). Studies with adult samples have supported this broadening effect (Estrada et al., 1997; Isen et al., 2000; Phillips et al., 2002). However, studies with children are limited to positive affect in general (Blau &amp; Klein, 2010; Greene &amp; Noice, 1988; Yates et al., 1981) and did not examine the thought-action repertoires of specific positive emotions. In this project, we investigate whether the positive emotion of amusement (1) expands the thought-action repertoire and (2) influences whether children are more likely to want to do something with other children. In addition, we consider the role of habitual differences in experiencing and expressing amusement (i.e., temperament) on the broadening effect (1 &amp; 2)

How was your child’s temperament today and last week? Considering within-person variability in the measurement of infant temperament

Infant temperament is usually considered biologically driven and a precursor of personality. Despite being conceived as trait measures, parent reports for assessing infant temperament use short timescales, for example, the past 7 days, implying variability in temperament traits' expressions. In two daily diary studies, we use the perspective of whole-trait theory to investigate whether infant temperament is observable on a daily basis and to what degree infant temperament varies within-person across days. In Study 1, N = 137 mothers of infants aged 6-18 months reported on their infant’s daily (state) temperament (median number of days: 8, total observations: 984). The results suggest a substantial within-person variation in daily infant temperament (ICCs: .41 to .54). Study 2 (N = 199 mothers, median number of days: 7, total observations: 1375) replicated these results on the variability in infant state temperament (ICCs: .41 to .51). In addition, infant state temperament was related to infant trait temperament. However, certain temperament items – primarily those assessing surgency – were frequently rated as not applicable and did not seem suitable for daily assessments. Across both studies, results indicate substantial within-person variability in daily infant temperament and a strong trait component