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4.
Nat Struct Mol Biol ; 26(10): 930-940, 2019 10.
Article in English | MEDLINE | ID: mdl-31570875

ABSTRACT

Studies of spliceosomal interactions are challenging due to their dynamic nature. Here we used spliceosome iCLIP, which immunoprecipitates SmB along with small nuclear ribonucleoprotein particles and auxiliary RNA binding proteins, to map spliceosome engagement with pre-messenger RNAs in human cell lines. This revealed seven peaks of spliceosomal crosslinking around branchpoints (BPs) and splice sites. We identified RNA binding proteins that crosslink to each peak, including known and candidate splicing factors. Moreover, we detected the use of over 40,000 BPs with strong sequence consensus and structural accessibility, which align well to nearby crosslinking peaks. We show how the position and strength of BPs affect the crosslinking patterns of spliceosomal factors, which bind more efficiently upstream of strong or proximally located BPs and downstream of weak or distally located BPs. These insights exemplify spliceosome iCLIP as a broadly applicable method for transcriptomic studies of splicing mechanisms.


Subject(s)
RNA Precursors/metabolism , Ribonucleoproteins, Small Nuclear/metabolism , Spliceosomes/metabolism , Cell Line , Humans , RNA Splice Sites , RNA Splicing , RNA-Binding Proteins/metabolism
6.
Community Ment Health J ; 55(6): 979-982, 2019 08.
Article in English | MEDLINE | ID: mdl-31102164

ABSTRACT

This study examined whether transitioning patients from oral antipsychotics (POs) to long-acting injectable antipsychotics (LAIs) helps patients achieve recovery-oriented goals. Data was extracted from San Francisco County's electronic medical record system for this retrospective pre-post observational study. Patients reflect a safety-net population treated in community-based mental health settings during 2015. The San Francisco Adult Strengths and Needs Assessment (SF ANSA), a measure of psychosocial functioning, was used to assess within-subject change when treated with POs versus LAIs. In our study sample (N = 77), LAI SF ANSA scores showed significant improvements in criminal behaviors (p = .017), medication adherence (p = .008), and spirituality (p = .028), and a non-significant trend for residential stability (p = .073). This is the first study to evaluate improvements in key psychosocial areas after treatment with LAIs. This work suggests that LAIs can be another tool for providers to help patients work towards their recovery-oriented goals.


Subject(s)
Antipsychotic Agents/therapeutic use , Schizophrenia/drug therapy , Adult , Aged , Criminal Behavior/drug effects , Female , Humans , Injections , Male , Middle Aged , Retrospective Studies , San Francisco , Treatment Outcome , Urban Population
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