Decision letter for "Screening method to identify hydrogel formulations that facilitate myotube formation from encapsulated primary myoblasts"

Atypical protein kinase Cζ (PKCζ) is emerging as a mediator of differentiation. Here, we describe a novel role for PKCζ in myogenic differentiation, demonstrating that PKCζ activity is indispensable for differentiation of both C2C12 and mouse primary myoblasts. PKCζ was found to be associated with and to regulate the Cdk5/p35 signaling complex, an essential factor for both neuronal and myogenic differentiation. Inhibition of PKCζ activity prevented both myotube formation and simultaneous reorganization of the nestin intermediate filament cytoskeleton, which is known to be regulated by Cdk5 during myogenesis. p35, the Cdk5 activator, was shown to be a specific phosphorylation target of PKCζ. PKCζ-mediated phosphorylation of Ser-33 on p35 promoted calpain-mediated cleavage of p35 to its more active and stable fragment, p25. Strikingly, both calpain activation and the calpain-mediated cleavage of p35 were shown to be PKCζ-dependent in differentiating myoblasts. Overall, our results identify PKCζ as a controller of myogenic differentiation by its regulation of the phosphorylation-dependent and calpain-mediated p35 cleavage, which is crucial for the amplification of the Cdk5 activity that is required during differentiation.

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An integrated screening method for evaluating the pulmonary toxicity of inhaled particulates: Role of microscopic techniques in assessing pulmonary macrophage clearance functions

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100161692 ◽

1990 ◽

Vol 48 (3) ◽

pp. 826-827

Author(s):

David B. Warheit ◽

Lena Achinko ◽

Mark A. Hartsky

Keyword(s):

Bronchoalveolar Lavage ◽

Pulmonary Toxicity ◽

Screening Method ◽

Pulmonary Response ◽

Inhaled Particles ◽

Cytochemical Analysis ◽

Pulmonary Macrophages ◽

Integrated Screening

There is a great need for the development of a rapid and reliable bioassay to evaluate the pulmonary toxicity of inhaled particles. A number of methods have been proposed, including lung clearance studies, bronchoalveolar lavage analysis, and in vitro cytotoxicity tests. These methods are often limited in scope inasmuch as they measure only one dimension of the pulmonary response to inhaled, instilled or incubated dusts. Accordingly, a comprehensive approach to lung toxicity studies has been developed.To validate the method, rats were exposed for 6 hours or 3 days to various concentrations of either aerosolized alpha quartz silica (Si) or carbonyl iron (CI) particles. Cells and fluids from groups of sham and dust-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, LDH and protein values were measured in BAL fluids at several time points postexposure. Cells were counted and evaluated for viability, as well as differential and cytochemical analysis. In addition, pulmonary macrophages (PM) were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy.

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Psychologists Search for Screening Method to Help Decide When Early-Alzheimer's Patients Should Stop Driving: Meta-Analysis of 27 Studies Showed Caregiver Reports May be Unreliable; Visuospatial Tests Were the Best Predictors of Driving Skill

PsycEXTRA Dataset ◽

10.1037/e480442006-001 ◽

2004 ◽

Author(s):

Keyword(s):

Meta Analysis ◽

Screening Method ◽

Driving Skill

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Is Colour Doppler Ultrasound a Sensitive Screening Method in Diagnosing Deep Vein Thrombosis after Hip Surgery ?

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650252 ◽

1996 ◽

Vol 75 (02) ◽

pp. 242-245 ◽

Cited By ~ 20

Author(s):

Marie Magnusson ◽

Bengt I Eriksson ◽

Peter Kãlebo ◽

Ramon Sivertsson

Keyword(s):

Deep Vein Thrombosis ◽

High Risk ◽

Doppler Ultrasound ◽

Predictive Value ◽

Screening Method ◽

Colour Doppler ◽

Vein Thrombosis ◽

Colour Doppler Ultrasound ◽

Asymptomatic Patients ◽

Deep Vein

SummaryPatients undergoing orthopedic surgery are at high risk of developing deep vein thrombosis. One hundred and thirty-eight consecutive patients undergoing total hip replacement or hip fracture surgery were included in this study. They were surveilled with colour Doppler ultrasound (CDU) and bilateral ascending contrast phlebography. The prevalence of proximal and distal DVT in this study was 5.8% and 20.3% respectively.CDU has a satisfactory sensitivity in patients with symptomatic deep vein thrombosis, especially in the proximal region. These results could not be confirmed in the present study of asymptomatic patients. The sensitivity was 62.5% (95% confidence interval: C.I. 24-91%) and the specificity 99.6% (C.I. 98-100%) for proximal DVT; 53.6% (C.I. 34-73%) and 98% (C.I. 96-99%) respectively for distal thrombi. The overall sensitivity was 58.1% (C.I. 39-75%) and the specificity 98% (C.I. 96-99%). The positive predictive value was 83.3% (C.I. 36-99%) and 75% (C.I. 51-91%) for proximal and distal DVT respectively. The negative predictive value was 98.9% (C.I. 98-100%) and 94.9% (C.I. 92-98%) for proximal and distal DVT respectively. The results of this study showed that even with a highly specialised and experienced investigator the sensitivity of CDU was too low to make it suitable for screening purposes in a high risk surgical population.

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The Diagnosis of Lupus Anticoagulants by the Activated Partial Thromboplastin Time - The Central Role of Phosphatidyl Serine

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661166 ◽

1984 ◽

Vol 52 (02) ◽

pp. 172-175 ◽

Cited By ~ 57

Author(s):

P R Kelsey ◽

K J Stevenson ◽

L Poller

Keyword(s):

Screening Method ◽

Coagulation Factors ◽

Phosphatidyl Serine ◽

Test System ◽

Specific Factor ◽

Marginal Effect ◽

Constant Composition ◽

Lupus Anticoagulants ◽

Different Types

SummaryLiposomes of pure phospholipids were used in a modified APTT test system and the role of phosphatidyl serine (PS) in determining the sensitivity of the test system to the presence of lupus anticoagulants was assessed. Six consecutive patients with lupus anticoagulants and seven haemophiliacs with anticoagulants directed at specific coagulation factors, were studied. Increasing the concentration of phospholipid in the test system markedly reduced the sensitivity to lupus anticoagulants but had marginal effect on the specific factor inhibitors. The same effect was achieved when the content of PS alone was increased in a vehicle liposome of constant composition.The results suggest that the lupus anticoagulants can best be detected by a screening method using an APTT test with a reagent of low PS content. The use of a reagent rich in PS will largely abolish the lupus anticoagulant’s effect on the APTT. An approach using the two different types of reagent may facilitate differentiation of lupus inhibitors from other types of anticoagulant.

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