can Society for Microbiology.Nuclear import of viral genomes is an important step during the life cycle of adenoviruses (AdV), requiring soluble cellular factors as well as proteins of the nuclear pore complex (NPC). We addressed the role of the cytoplasmic nucleoporin Nup358 during adenoviral genome delivery by performing depletion/reconstitution experiments and time resolved quantification of adenoviral genome import. Nup358-depleted cells displayed reduced nuclear import efficiencies of adenoviral genomes and the nuclear import receptor transportin 1 became rate-limiting under these conditions. Furthermore, we identified a minimal N-terminal region of Nup358 that was sufficient to compensate the import defect. Our data support a model where Nup358 functions as an assembly platform that promotes the formation of transport complexes, allowing AdV to exploit a physiological protein import pathway for accelerated transport of its DNA.IMPORTANCE Nuclear import of viral genomes is an essential step to initiate productive infection for several nuclear replicating DNA viruses. On the other hand, DNA is not a physiological nuclear import substrate and consequently, viruses have to exploit existing physiological transport routes. Here we show that adenoviruses use the nucleoporin Nup358 to increase the efficiency of adenoviral genome import. In its absence, genome import efficiency is reduced and the transport receptor transportin 1 becomes rate limiting. We show that the N-terminal half of Nup358 is sufficient to drive genome import and identify a transportin 1 binding region. In our model, adenovirus genome import exploits an existing protein import pathways and Nup358 serves as an assembly platform for transport complexes. Copyright © 2020 American Society for Microbiology.Human leukocyte antigen (HLA) B*5101 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are strongly genetically associated with Behçet's disease (BD).  Previous studies have defined two subgroups of HLA-B*51 peptidome containing Proline (Pro) or Alanine (Ala) at position 2 (P2).  Little is known about the unconventional non-Pro/Ala2 HLA-B*51-bound peptides.  We aimed to study the features of this novel sub-peptidome, and investigate its regulation by ERAP1.  CRISPR-Cas9 was used to generate an HLA-ABC-triple knockout HeLa cell line (HeLa.ABC-KO), which was subsequently transduced to express HLA-B*5101 (HeLa.ABC-KO.B51).  ERAP1 was silenced using lentiviral shRNA.  Peptides bound to HLA-B*5101 were eluted and analyzed by Mass Spectrometry.  The characteristics of non-Pro/Ala2, Pro2 and Ala2 peptides, and their alteration by ERAP1 silencing were investigated.  Effects of ERAP1 silencing on cell surface expression of HLA-B*5101 were studied using flow cytometry.  More than 20% of peptides eluted from HLA-B*5101ecting the risk of developing BD. This has implications for theories of disease pathogenesis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.INTRODUCTION Little is known about how changes in physiologic parameters affect venous sinus pressure measurements, waveforms, or gradients associated with sinus stenosis. OBJECTIVE To evaluate the effect of changes in cardiovascular and respiratory physiologic parameters on venous sinus pressure and caliber measurements in patients with idiopathic intracranial hypertension (IIH) undergoing venous sinus stenting. METHODS In a prospective, randomized pilot study, eight patients with IIH undergoing venous sinus stenting were randomized to one of two groups. Under general anesthesia, patients underwent venous manometry and waveform recordings twice in succession based on assigned physiologic groups immediately before stenting. The mean arterial pressure (MAP) group maintained normocapnia but modified MAPs in two arms to control for temporal confounding group A1 (MAP 60-80 mm Hg then 100-110 mm Hg) and group A2 (MAP 100-110 mm Hg then 60-80 mm Hg). The end-tidal carbon dioxide (EtCO2) group maintained a high-normnd permissions. Published by BMJ.OBJECTIVE The aim of this study was to systematically and simultaneously examine the association of intrinsic and extrinsic motivating factors with physician burnout and job dissatisfaction. DESIGN A nationally representative survey was fielded from September to November 2017. SETTING Hospitals and clinics throughout Taiwan. PARTICIPANTS A total of 6674 physicians. MAIN EXPOSURE MEASURE The main exposure measures were intrinsic motivators (sense of calling, personally rewarding hours per day and meaningful, long-term relationships with patients) and extrinsic motivators (income, work hours, autonomy, and pay-for-performance (P4P) and bundled payment initiatives). MAIN OUTCOME MEASURES The main outcome measures were physician burnout and job dissatisfaction. RESULTS A total of 1152 physicians returned the surveys. More sense of calling and personally rewarding hours per day were associated with less physician burnout (OR 0.16, 95% CI 0.10 to 0.26 and OR 0.25, 95% CI 0.13 to 0.47, respectively) and job dissatistted under CC BY-NC. Auranofin in vitro No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION In order to properly evaluate the efficacy of orthopaedic procedures, rigorous, randomised controlled sham surgery trial designs are necessary. However, randomised controlled trials (RCTs) for surgery involving a placebo are ethically debated and difficult to conduct with many failing to reach their desired sample size and power. A review of the literature on barriers and enablers to recruitment, and patient and surgeon attitudes and preferences towards sham surgery trials, will help to determine the characteristics necessary for successful recruitment. METHODS AND ANALYSIS This review will scope the diverse literature surrounding sham surgery trials with the aim of informing a discrete choice experiment to empirically test patient and surgeon preferences for different sham surgery trial designs. The scoping review will be conducted in accordance with the methodological framework described in Arksey and O'Malley (2005) and reported using the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols extension for Scoping Reviews.