Rtp1p Is a Karyopherin-Like Protein Required for RNA Polymerase II Biogenesis

The assembly and nuclear transport of RNA polymerase II (RNA pol II) are processes that require the participation of many auxiliary factors. In a yeast genetic screen, we identified a previously uncharacterized gene, YMR185w (renamed RTP1), which encodes a protein required for the nuclear import of RNA pol II. Using protein affinity purification coupled to mass spectrometry, we identified interactions between Rtp1p and members of the R2TP complex. Rtp1p also interacts, to a different extent, with several RNA pol II subunits. The pattern of interactions is compatible with a role for Rtp1p as an assembly factor that participates in the formation of the Rpb2/Rpb3 subassembly complex and its binding to the Rpb1p-containing subcomplex. Besides, Rtp1p has a molecular architecture characteristic of karyopherins, composed of HEAT repeats, and is able to interact with phenylalanine-glycine-containing nucleoporins. Our results define Rtp1p as a new component of the RNA pol II biogenesis machinery that plays roles in subunit assembly and likely in transport through the nuclear pore complex

Addressing climate change with behavioral science: a global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors

A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis

BACKGROUND: Absent T-cell immunity resulting in life-threatening infections provides a clear rationale for hematopoetic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency (SCID). Combined immunodeficiencies (CIDs) and "atypical" SCID show reduced, not absent T-cell immunity. If associated with infections or autoimmunity, they represent profound combined immunodeficiency (P-CID), for which outcome data are insufficient for unambiguous early transplant decisions. // OBJECTIVES: We sought to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. // METHODS: In this prospective and retrospective observational study, we recruited nontransplanted patients with P-CID aged 1 to 16 years to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. // RESULTS: A total of 51 patients were recruited (median age, 9.6 years). Thirteen of 51 had a genetic diagnosis of "atypical" SCID and 14 of 51 of CID. About half of the patients had less than 10% naive T cells, reduced/absent T-cell proliferation, and at least 1 significant clinical event/year, demonstrating their profound immunodeficiency. Nineteen patients (37%) underwent transplantation within 1 year of enrolment, and 5 of 51 patients died. Analysis of the HSCT decisions revealed the anticipated heterogeneity, favoring an ongoing prospective matched-pair analysis of patients with similar disease severity with or without transplantation. Importantly, so far neither the genetic diagnosis nor basic measurements of T-cell immunity were good predictors of disease evolution. // CONCLUSIONS: The P-CID study for the first time characterizes a group of patients with nontypical SCID T-cell deficiencies from a therapeutic perspective. Because genetic and basic T-cell parameters provide limited guidance, prospective data from this study will be a helpful resource for guiding the difficult HSCT decisions in patients with P-CID

Hair-based rapid analyses for multiple drugs in forensics and doping : application of dynamic multiple reaction monitoring with LC-MS/MS

This is the first report of the application of this proprietary system to investigate the presence of drugs in human hair samples. The method is selective, sensitive and robust for the screening and confirmation of multiple drugs in a single analysis and has potential as a very useful tool for the analysis of large array of controlled substances and drugs of abuse

Current practice of transitional care for adolescents and young adults in Swiss paediatric and adult rheumatology centres.

About half of all children with rheumatic diseases need continuous medical care during adolescence and adulthood. A good transition into adult rheumatology is essential. Guidelines for a structured transition process have therefore been recommended by the European League Against Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PReS). However, implementation of these guidelines requires resources often not available in a busy clinical practice. To assess the current practice of transitional care in Switzerland in relation to EULAR/PReS recommendations and to describe gaps and challenges in following the recommendations. All paediatric Swiss rheumatology centres and their collaborating adult centres offering a transition service to adult care were invited to participate in this survey. The responsible paediatric and adult rheumatologist of each centre was interviewed separately using a structured manual addressing the EULAR/PReS transitional care recommendations. All 10 paediatric and 9 out of 10 adult rheumatologists agreed to participate. Centres varied in the number of patients in transition, from n = 0 to n = 111. The following EULAR/PReS recommendations were implemented and applied in most centres: continuity in the healthcare team, consultations focused on adolescents and young adults, joint consultations between the paediatric and adult rheumatologist, and access to the EULAR website. Only rarely did a centre have a written transition policy or evaluate their transitional care programme. The vast majority of the interviewees had no specific training in adolescent health. Most centres rated their transitional care performance as very good. Transition in Switzerland is not uniform and consequently the implementation of the EULAR/PReS recommendations is variable in Swiss rheumatology centres. Skills of healthcare professionals, continuity between clinical settings, size of the centres, and hospital focus on the needs of adolescents and young adults may represent key predictors of successful transitional care for patients with chronic rheumatic diseases. Future studies should examine these variables