The nuclear and subnuclear compartmentalization of the telomerase-associated protein and H/ACA ribonucleoprotein component dyskerin is an important although incompletely understood aspect of H/ACA ribonucleoprotein function. Four SUMOylation sites were previously identified in the C-terminal nuclear/nucleolar localization signal (N/NoLS) of dyskerin. We found that a cytoplasmic localized C-terminal truncation variant of dyskerin lacking most of the C-terminal N/NoLS represents an under-SUMOylated variant of dyskerin compared to wild-type dyskerin. We demonstrate that mimicking constitutive SUMOylation of dyskerin using a SUMO3 fusion construct can drive nuclear accumulation of this variant and that the SUMO site K467 in this N/NoLS is particularly important for the subnuclear localization of dyskerin to the nucleolus in a mature H/ACA complex assembly- and SUMO-dependent manner. We also characterize a novel SUMO-interacting motif in the mature H/ACA complex component GAR1 that mediates the interaction between dyskerin and GAR1. Mislocalization of dyskerin, either in the cytoplasm or excluded from the nucleolus, disrupts dyskerin function and leads to reduced interaction of dyskerin with the telomerase RNA. These data indicate a role for dyskerin C-terminal N/NoLS SUMOylation in regulating the nuclear and subnuclear localization of dyskerin, which is essential for dyskerin function as both a telomerase-associated protein and as an H/ACA ribonucleoprotein.IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffolding protein that is overexpressed in a number of cancers, including liver cancer, and is associated with protumorigenic processes, such as cell proliferation, motility, and adhesion. IQGAP1 can integrate multiple signaling pathways and could be an effective antitumor target. Therefore, we examined the role of IQGAP1 in tumor initiation and promotion during liver carcinogenesis. We found that ectopic overexpression of IQGAP1 in the liver is not sufficient to initiate tumorigenesis. Moreover, we report that the tumor burden and cell proliferation in the diethylnitrosamine-induced liver carcinogenesis model in Iqgap1-/- mice may be driven by MET signaling. In contrast, IQGAP1 overexpression enhanced YAP activation and subsequent NUAK2 expression to accelerate and promote hepatocellular carcinoma (HCC) in a clinically relevant model expressing activated (S45Y) β-catenin and MET. Here, increasing IQGAP1 expression in vivo does not alter β-catenin or MET activation; instead, it promotes YAP activity. Overall, we demonstrate that although IQGAP1 expression is not required for HCC development, the gain of IQGAP1 function promotes the rapid onset and increased liver carcinogenesis. Our results show that an adequate amount of IQGAP1 scaffold is necessary to maintain the quiescent status of the liver.SHOC2 is a prototypical leucine-rich repeat protein that promotes downstream receptor tyrosine kinase (RTK)/RAS signaling and plays important roles in several cellular and developmental processes. Gain-of-function germ line mutations of SHOC2 drive the RASopathy Noonan-like syndrome, and SHOC2 mediates adaptive resistance to mitogen-activated protein kinase (MAPK) inhibitors. Similar to many scaffolding proteins, SHOC2 facilitates signal transduction by enabling proximal protein interactions and regulating the subcellular localization of its binding partners. Here, we review the structural features of SHOC2 that mediate its known functions, discuss these elements in the context of various binding partners and signaling pathways, and highlight areas of SHOC2 biology where a consensus view has not yet emerged.Clinicians and lay people tend to overestimate the effectiveness of a treatment when only the relative effect is presented, particularly if the relative effect is large, but the absolute effect is small. In recognition of this problem, item 17b of The Consolidated Standards of Reporting Trials (CONSORT) 2010 statement stipulates authors present both absolute and relative effects for binary outcomes in randomised controlled trials (RCTs). https://www.selleckchem.com/products/ho-3867.html Adherence to item 17b and the effect of differing levels of CONSORT endorsement by journals on adherence is not well known. We assessed the extent to which item 17b is adhered to in 258 RCTs published in five leading medical journals (Annals of Internal Medicine, BMJ, JAMA, The Lancet and The New England Journal of Medicine) between January and December 2019 that all endorsed the CONSORT statement to varying degrees. Only 53 of 258 (20.5%; 95% CI 15.8% to 26.0%) included studies adhered fully to item 17b. Proportional adherence was higher in journals that endorsed the statement more strictly (BMJ and JAMA, 47.4% [34.0% to 61.0%]) compared with journals less strict in their endorsement (NEJM and Ann Intern Med, 12.2% [7.0% to 19.3%]; The Lancet, 14.1% [7.3% to 23.8%]). Journals that only recommend author adherence to CONSORT had a greater proportion of studies reporting only relative effects in the main results section (62.6%) and abstract (64.2%) compared with journals that require authors to submit a completed checklist (24.6% and 29.8%, respectively). The majority of RCTs (79.5%) with binary primary outcomes published in five leading medical journals during 2019 do not report both absolute and relative effect estimates as per item 17b of the CONSORT guideline despite its universal endorsement. Differences in adherence were observed between journals that endorsed the CONSORT statement to differing extents.Delirium is a serious and common condition that leads to significant adverse health outcomes for hospitalised older adults. It occurs in 30%-55% of patients with hip fractures and is one of the most common postoperative complications in older adults undergoing orthopaedic surgery. Multicomponent, non-pharmacological interventions can reduce delirium incidence by up to 30% but are often challenging to implement as part of routine care. We identified a gap in the delivery of non-pharmacological interventions on an orthopaedic unit. This project aimed to implement a bedside sign on an orthopaedic unit to reduce the occurrence of delirium by prompting staff to use multicomponent evidence-based delirium prevention strategies for at-risk older adults. Quality improvement methods were used to integrate and optimise the use of a bedside 'delirium prevention' sign on an orthopaedic unit.The sign was implemented in four target rooms and sign completion rates increased from 47% to 83% (95% CI 71.7% to 94.9%; p less then 0.