Stress-induced nuclear speckle reorganization is linked to activation of immediate early gene splicing.

Current models posit that nuclear speckles (NSs) serve as reservoirs of splicing factors and facilitate posttranscriptional mRNA processing. Here, we discovered that ribotoxic stress induces a profound reorganization of NSs with enhanced recruitment of factors required for splice-site recognition, including the RNA-binding protein TIAR, U1 snRNP proteins and U2-associated factor 65, as well as serine 2 phosphorylated RNA polymerase II. NS reorganization relies on the stress-activated p38 mitogen-activated protein kinase (MAPK) pathway and coincides with splicing activation of both pre-existing and newly synthesized pre-mRNAs. In particular, ribotoxic stress causes targeted excision of retained introns from pre-mRNAs of immediate early genes (IEGs), whose transcription is induced during the stress response. Importantly, enhanced splicing of the IEGs ZFP36 and FOS is accompanied by relocalization of the corresponding nuclear mRNA foci to NSs. Our study reveals NSs as a dynamic compartment that is remodeled under stress conditions, whereby NSs appear to become sites of IEG transcription and efficient cotranscriptional splicing.

Five years after PACIFIC: update on multimodal treatment efficacy based on real-world reports.

INTRODUCTION: The growing body of real-life data on maintenance treatment with durvalumab suggests that immunological markers of the cancer host interplay may have significant effects on the efficacy of multimodal therapy in patients with unresectable stage III NSCLC. AREAS COVERED: We summarize real-world clinical data regarding this new tri-modal approach and report on potential biomarker landscape. EXPERT OPINION: The obvious question posed in this context of a very heterogeneous inoperable stage III NSCLC disease is: How can we augment an ability to predict checkpoint inhibition success or failure? Which tools and biomarkers, which clinical metadata and genetic background are relevant and feasible? No single biomarker will ever fully dominate the unresectable stage III NSCLC space, so we advocate multilevel and multivariate analysis of biomarkers. In this particular opinion piece, we explore the impact of PD-L1 expression on tumor cells, neutrophil-to-lymphocyte ratio, EGFR and STK11 mutational status, interferon-gamma signature, and tumor-infiltrating lymphocytes among others.

A Single-Day Training for Managers Reduces Cognitive Stigma Regarding Mental Health Problems: A Randomized Trial.

BACKGROUND: Mental illnesses have received increasing attention in the work context in recent years, yet they are still often accompanied by stigma. One starting point for stigma reduction is interventions in the workplace. The present study evaluated a one-day workshop for managers in a large company. METHOD: Enrolled managers (n = 70) were randomly assigned to the intervention group and the waiting control group. The training included a theoretical section on mental and stress-related diseases as well as the interplay between work and health, group work on personal stress experience, theoretical input on dealing with mentally ill employees, and a group discussion on this topic along with case studies. Both groups completed the following questionnaires at baseline and three months after training: Effort-Reward Imbalance Questionnaire, Patient Health Questionnaire, Mental Health Knowledge Schedule, Social Distance Scale, and the Irritation Scale. RESULTS: Compared to the waiting group, the intervention group showed a significant improvement in the Mental Health Knowledge Schedule (U = 417.00, p = 0.040) and an increase in the Irritation Scale (U = 371.50 p = 0.011). All other scales remained unchanged. CONCLUSION: The content and duration of the training were adequate to reduce cognitive stigma towards mental illness. However, the present approach was not sufficient for an improvement in the subjective stress level of the participating managers.

The Interaction Between Text Modality and the Learner's Modality Preference Influences Comprehension and Cognitive Load.

This study investigates the aptitude-treatment interaction between text modality and learners' modality preference on learning outcomes and cognitive load, which is currently a point of controversy. The Meshing Hypothesis postulates there are better learning outcomes when the modality of a learning environment matches the learner's preference. However, previous research supporting the Meshing Hypothesis shows methodological issues. Therefore, clear empirical support is needed. We tested 42 learners in a between-subject design: Their preferences were either auditive-ambiguous or visual, and half of each preference group randomly learned either with an auditive or a visual text. As expected, we did not find any main effects, but a significant interaction between the text modality and the learner's preference for comprehension outcomes, extraneous cognitive load, and germane cognitive load. Specifically, learners with a preference for visual texts benefit from learning with their preferred modality, they showed higher comprehension scores and less extraneous load when learning from a visual text. Auditive-ambiguous learners showed almost equal results with both text modalities. This might be explained by the fact that most texts in everyday life are presented visually, and therefore learners with an auditive preference needed to develop appropriate reading strategies. Thus, our results partly support the Meshing Hypothesis.

The Influence of Background Music on Learning in the Light of Different Theoretical Perspectives and the Role of Working Memory Capacity.

This study investigates how background music influences learning with respect to three different theoretical approaches. Both the Mozart effect as well as the arousal-mood-hypothesis indicate that background music can potentially benefit learning outcomes. While the Mozart effect assumes a direct influence of background music on cognitive abilities, the arousal-mood-hypothesis assumes a mediation effect over arousal and mood. However, the seductive detail effect indicates that seductive details such as background music worsen learning. Moreover, as working memory capacity has a crucial influence on learning with seductive details, we also included the learner's working memory capacity as a factor in our study. We tested 81 college students using a between-subject design with half of the sample listening to two pop songs while learning a visual text and the other half learning in silence. We included working memory capacity in the design as a continuous organism variable. Arousal and mood scores before and after learning were collected as potential mediating variables. To measure learning outcomes we tested recall and comprehension. We did not find a mediation effect between background music and arousal or mood on learning outcomes. In addition, for recall performance there were no main effects of background music or working memory capacity, nor an interaction effect of these factors. However, when considering comprehension we did find an interaction between background music and working memory capacity: the higher the learners' working memory capacity, the better they learned with background music. This is in line with the seductive detail assumption.

Can Music Foster Learning - Effects of Different Text Modalities on Learning and Information Retrieval.

This study investigates the possibilities of fostering learning based on differences in recall and comprehension after learning with texts which were presented in one of three modalities: either in a spoken, written, or sung version. All three texts differ regarding their processing, especially when considering working memory. Overall, we assume the best recall performance after learning with the written text and the best comprehension performance after learning with the sung text, respectively, compared to both other text modalities. We also analyzed whether the melody of the sung material functions as a mnemonic aid for the learners in the sung text condition. If melody and text of the sung version are closely linked, presentation of the melody during the post-test phase could foster text retrieval. 108 students either learned from a sung text performed by a professional singer, a printed text, or the same text read out loud. Half of the participants worked on the post-test while listening to the melody used for the musical learning material and the other half did not listen to a melody. The written learning modality led to significantly better recall than with the spoken (d = 0.97) or sung text (d = 0.78). However, comprehension after learning with the sung modality was significantly superior compared to when learning with the written learning modality (d = 0.40). Reading leads to more focus on details, which is required to answer recall questions, while listening fosters a general understanding of the text, leading to higher levels of comprehension. Listening to the melody during the post-test phase negatively affected comprehension, irrespective of the modality during the learning phase. This can be explained by the seductive detail effect, as listening to the melody during the post-test phase may distract learners from their main task. In closing, theoretical and practical implications are discussed.