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In humans and other holozoan organisms, the ribosomal protein eS30 is synthesized as a fusion protein with the ubiquitin-like protein FUBI. However, FUBI is not part of the mature 40S ribosomal subunit and cleaved off by an as-of-yet unidentified protease. How FUBI-eS30 processing is coordinated with 40S subunit maturation is unknown. To study the mechanism and importance of FUBI-eS30 processing, we expressed non-cleavable mutants in human cells, which affected late steps of cytoplasmic 40S maturation, including the maturation of 18S rRNA and recycling of late-acting ribosome biogenesis factors. Differential affinity purification of wild-type and non-cleavable FUBI-eS30 mutants identified the deubiquitinase USP36 as a candidate FUBI-eS30 processing enzyme. Depletion of USP36 by RNAi or CRISPRi indeed impaired FUBI-eS30 processing and moreover, purified USP36 cut FUBI-eS30 in vitro. Together, these data demonstrate the functional importance of FUBI-eS30 cleavage and identify USP36 as a novel protease involved in this process.

Establishment of translational competence represents a decisive cytoplasmic step in the biogenesis of 40S ribosomal subunits. This involves final 18S rRNA processing and release of residual biogenesis factors, including the protein kinase RIOK1. To identify novel proteins promoting the final maturation of human 40S subunits, we characterized pre-ribosomal subunits trapped on RIOK1 by mass spectrometry, and identified the deubiquitinase USP16 among the captured factors. We demonstrate that USP16 constitutes a component of late cytoplasmic pre-40S subunits that promotes the removal of ubiquitin from an internal lysine of ribosomal protein RPS27a/eS31. USP16 deletion leads to late 40S subunit maturation defects, manifesting in incomplete processing of 18S rRNA and retarded recycling of late-acting ribosome biogenesis factors, revealing an unexpected contribution of USP16 to the ultimate step of 40S synthesis. Finally, ubiquitination of RPS27a appears to depend on active translation, pointing at a potential connection between 40S maturation and protein synthesis.

Eukaryotic ribosomes consist of a small 40S and a large 60S subunit that are assembled in a highly coordinated manner. More than 200 factors ensure correct modification, processing and folding of ribosomal RNA and the timely incorporation of ribosomal proteins 1 , 2 . Small subunit maturation ends in the cytosol, when the final rRNA precursor, 18S-E, is cleaved at site 3 by the endonuclease NOB1 3 . Previous structures of human 40S precursors have shown that NOB1 is kept in an inactive state by its partner PNO1 4 . The final maturation events, including the activation of NOB1 for the decisive rRNA-cleavage step and the mechanisms driving the dissociation of the last biogenesis factors have, however, remained unresolved. Here we report five cryo-electron microscopy structures of human 40S subunit precursors, which describe the compositional and conformational progression during the final steps of 40S assembly. Our structures explain the central role of RIOK1 in the displacement and dissociation of PNO1, which in turn allows conformational changes and activation of the endonuclease NOB1. In addition, we observe two factors, eukaryotic translation initiation factor 1A domain-containing protein (EIF1AD) and leucine-rich repeat-containing protein 47 (LRRC47), which bind to late pre-40S particles near RIOK1 and the central rRNA helix 44. Finally, functional data shows that EIF1AD is required for efficient assembly factor recycling and 18S-E processing. Our results thus enable a detailed understanding of the last steps in 40S formation in human cells and, in addition, provide evidence for principal differences in small ribosomal subunit formation between humans and the model organism Saccharomyces cerevisiae . Studies of five cryo-electron microscopy structures reveal the composition and conformational progression in the final maturation events of human 40S ribosomal subunit assembly.

In humans and other holozoan organisms, the ribosomal protein eS30 is synthesized as a fusion protein with the ubiquitin-like protein FUBI. However, FUBI is not part of the mature 40S ribosomal subunit and cleaved off by an as-of-yet unidentified protease. How FUBI-eS30 processing is coordinated with 40S subunit maturation is unknown. To study the mechanism and importance of FUBI-eS30 processing, we expressed non-cleavable mutants in human cells, which affected late steps of cytoplasmic 40S maturation, including the maturation of 18S rRNA and recycling of late-acting ribosome biogenesis factors. Differential affinity purification of wild-type and non-cleavable FUBI-eS30 mutants identified the deubiquitinase USP36 as a candidate FUBI-eS30 processing enzyme. Depletion of USP36 by RNAi or CRISPRi indeed impaired FUBI-eS30 processing and moreover, purified USP36 cut FUBI-eS30 in vitro. Together, these data demonstrate the functional importance of FUBI-eS30 cleavage and identify USP36 as a novel protease involved in this process.

Background: Compared to the general German population, refugees in Germany are a high-risk group for trauma spectrum disorders. Currently, many barriers exist for the implementation of a screen-and-treat approach for mental disorders as part of the routine health care provision during the early stage of the immigration process. Objective: The aim of the present study was to develop and test a systematic screening approach to identify individual refugees in need of mental health care during the initial immigration phase. Method: 167 newly arrived refugees underwent a screening interview with the Refugee Health Screener (RHS) carried out by Intercultural Therapy Assistants (ITAs). The ITAs were super­vised by psychologists at a reception centre in Bielefeld, Germany. A subsample of 48 persons partici­pated in clinical validation interviews. Results: Findings demonstrated the need for and feasibility of a systematic screening during the initial immigration phase. However, established cut-off values of the RHS had to be adapted and the screening procedure had to be adjusted due to the needs of a significant number of refugees in severe psychological crises. Conclusion: A systematic screening that is applied shortly after arrival facilitates the early identification of refugees at risk of developing mental disorders and may be helpful to prevent chronic symptom development and an aggravation of psychological crises. A systematic complementary screening procedure during the initial immigration phase was found to be useful for the identification of refugees in need of mental health care. The procedure could be implemented both safely and efficiently in conjunction with the initial medical check-up for recently arrived refugees. Responding to the needs of the refugees immediately following their arrival in Germany, we adjusted the cut-off of the screening instrument and suggest to explicitly include a detection procedure for severe psychological crises.

The focus of this study was to investigate primary school students’ achievement in the domain of measurement. We analyzed a large-scale data set ( N  = 6,638) from German third and fourth graders (8- to 10-year-olds). These data were collected in 2007 within the framework of the ESMaG (Evaluation of the Standards in Mathematics in Primary School) project carried out by the Institute for Educational Quality Improvement (IQB) at Humboldt University, Berlin, Germany. The data were interpreted using a classification scheme based on a conceptual–procedural distinction in measurement competence. The analyses with this classification revealed that grade, gender, and in particular figural reasoning ability are significantly related to overall measurement competence as well as on the sub-competencies of Instrumental knowledge and Measurement sense. The paper concludes with a discussion of the implications of the findings of this study for teaching and assessing measurement.