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Multisite phosphorylation of C-Nap1 releases it from Cep135 to trigger centrosome disjunction
Hardy, Tara,Lee, Miseon,Hames, Rebecca S.,Prosser, Suzanna L.,Cheary, Donna-Marie,Samant, Mugdha D.,Schultz, Francisca,Baxter, Joanne E.,Rhee, Kunsoo,Fry, Andrew M. The Company of Biologists 2014 Journal of cell science Vol.127 No.11
<P><B>ABSTRACT</B></P><P>During mitotic entry, centrosomes separate to establish the bipolar spindle. Delays in centrosome separation can perturb chromosome segregation and promote genetic instability. However, interphase centrosomes are physically tethered by a proteinaceous linker composed of C-Nap1 (also known as CEP250) and the filamentous protein rootletin. Linker disassembly occurs at the onset of mitosis in a process known as centrosome disjunction and is triggered by the Nek2-dependent phosphorylation of C-Nap1. However, the mechanistic consequences of C-Nap1 phosphorylation are unknown. Here, we demonstrate that Nek2 phosphorylates multiple residues within the C-terminal domain of C-Nap1 and, collectively, these phosphorylation events lead to loss of oligomerization and centrosome association. Mutations in non-phosphorylatable residues that make the domain more acidic are sufficient to release C-Nap1 from the centrosome, suggesting that it is an increase in overall negative charge that is required for this process. Importantly, phosphorylation of C-Nap1 also perturbs interaction with the core centriolar protein, Cep135, and interaction of endogenous C-Nap1 and Cep135 proteins is specifically lost in mitosis. We therefore propose that multisite phosphorylation of C-Nap1 by Nek2 perturbs both oligomerization and Cep135 interaction, and this precipitates centrosome disjunction at the onset of mitosis.</P>
Allergy, hypersensitivity and cosmetics
( Joan Hardy ) 대한화장품학회 1973 대한화장품학회지 Vol.3 No.1
The difficulties of immunological nomenclature are discussed, the term ALLERGY defined and the various types of HYPERSENSITIVITY reactions are listed and characterized. Evidence for the association of Type I and Type 11 hypersensitivity reactions with COSMETICS is discussed. A table of cosmetic ingredients which have been implicated as SENSITlZERS are given. PREDICTIVE PATCH TESTS for contact sensitizers on GUINEA-PIGS and man are evaluated. The difficulties of testing for ALLERGENS likely to produce Type I hypersensitivity are discussed. IN VITRO tests for sensitizers are mentioned. The' failure of all standard tests in the detection of weak sensitizers is emphasized.
The Influence of Health Perception on Shoulder Outcome Measure Scores
Richard E. Hardy,Engin Sungur,Christopher Butler,Jefferson C. Brand 대한견주관절학회 2019 대한견주관절의학회지 Vol.22 No.4
Background: Patient reported outcome measures assess clinical progress from the patient’s perspective. This study explored the relationship between shoulder outcome measures (The Disability of the Arm, Shoulder and Hand [DASH], American Shoulder and Elbow Surgeons Standard Shoulder Assessment score [ASES], and Constant score) by comparing the best possible scores obtained in an asymptomatic population compared to overall perception of health, as measured by the SF-36 outcome measure. Methods: Volunteers (age range, 20–69 years) with asymptomatic shoulders and no history of shoulder pain, injury, surgery, imaging, or pathology (bilaterally) were included. The DASH and ASES measures were completed by 111 volunteers (72 female, 39 male), of which 92 completed the Constant score (56 female, 36 male). The SF-36 was completed by all volunteers (level of evidence: IV case series). Results: The mean (x) score for ASES measure on the right shoulder was higher for the left-hand dominant side (x=100.00 vs. 95.02, p-value<0.001); no other significant differences. Better SF-36 scores were associated with better DASH scores. Our prediction models suggest that perception of overall health affects the DASH scores. Sex affected all three shoulder measures scores. Conclusions: Comparing scores of shoulder outcome measures to the highest possible score is not the most informative way to interpret patient progress. Variables such as health status, sex, and hand dominance need to be considered. Furthermore, it is possible to use these variables to predict scores of outcome measures, which facilitates the healthcare provider to deliver individualized care to their patients.