Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages

Cbl is a cytosolic protein that is rapidly tyrosine phosphorylated in response to Fc receptor activation and binds to the adaptor proteins Grb2, CrkL, and Nck. A few reports describe Cbl interactions in primary human hematopoietic cells. We show evidence that Cbl participates in signaling initiated by Fc gammaRI receptor cross-linking in human primary macrophages, and functions downstream of Src family kinases in this pathway. Fc gammaRI stimulation in human macrophages was associated with rapid and transient tyrosine phosphorylation of the Cbl adaptor protein. Immunoprecipitated Cbl was complexed with several tyrosine phosphorylated proteins, the most prominent of which was a 38-kDa band identified as the CrkL adaptor protein. CrkL associated with tyrosine-phosphorylated Cbl and itself became tyrosine phosphorylated after Fc gammaRI cross-linking. SLP-76, a recently cloned Grb2-associated protein, was strongly tyrosine phosphorylated after Fc gammaRI stimulation and was associated with both Cbl and Grb2. Grb2 and Cbl binding to SLP-76 were inducible after Fc gammaRI stimulation of the macrophages. Nck was inducibly bound to Cbl after Fc gammaRI stimulation, whereas Grb2 was constitutively associated with it. Shc was also inducibly tyrosine phosphorylated and bound to Grb2 after Fc gammaRI stimulation of the macrophages. PP1, a specific inhibitor of Src kinases, inhibited the Fc gammaRI-induced respiratory burst, as well as the tyrosine phosphorylation of Cbl and its inducible association with CrkL. These results suggest a fundamental role for the tyrosine phosphorylation of Cbl, CrkL, SLP-76, and Shc and the association of Cbl with CrkL, SLP-76, and Nck in Fc gammaRI signaling in human macrophages. Experiments performed with PP1, the specific Src kinase inhibitor, demonstrate the first evidence that Cbl and the Cbl-Crkl interaction are downstream targets for myeloid Src kinases required for the activation of myeloid NADPH oxidase activity.     

Pallister-Hall syndrome associated with an unbalanced chromosome translocation

We report 3 cases of Pallister-Hall syndrome involving hypothalamic hamartoblastoma, hypopituitarism, cranial, and limb abnormalities. The first 2 cases represent the first apparent sibs reported with this syndrome. Patient 1 represents the first known patient with this syndrome with an abnormal karyotype.     

Natural Convection Heat Transfer in a Porous Cavity with Sinusoidal Temperature Distribution Using Cu/Water Nanofluid: Double MRT Lattice Boltzmann Method

In this study, natural convection flow in a porous cavity with sinusoidal temperature distribution has been analyzed by a new double multi relaxation time (MRT) Lattice Boltzmann method (LBM). We consider a copper/water nanofluid filling a porous cavity. For simulating the temperature and flow fields, D2Q5 and D2Q9 lattices are utilized respectively, and the effects of different Darcy numbers (Da) (0.001-0.1) and various Rayleigh numbers (Ra) ($10^3$-$10^5$) for porosity ($ε$) between 0.4 and 0.9 have been considered. Phase deviation ($θ$) changed from 0 to $π$ and the volume fraction of nanoparticles (Ø) varied from 0 to 6%. The present results show a good agreement with the previous works, thus confirming the reliability the new numerical method proposed in this paper. It is indicated that the heat transfer rate increases at increasing Darcy number, porosity, Rayleigh number, the volume fraction of nanoparticles and phase deviation. However, the most sensitive parameter is the Rayleigh number. The maximum Nusselt deviation is 10%, 32% and 33% for Ra=$10^3$, $10^4$ and $10^5$, respectively, with $ε = 0.4$ to $ε = 0.9$. It can be concluded that the effect of Darcy number on the heat transfer rate increases at increasing Rayleigh number, yielding a maximum enhancement of the average Nusselt number around 12% and 61% for Ra=$10^3$ and Ra=$10^5$, respectively.     

Antibacterial Effects of Cinnamon: From Farm to Food,Cosmetic and Pharmaceutical Industries

Herbs and spices have been used since ancient times, because of their antimicrobial properties increasing the safety and shelf life of food products by acting against foodborne pathogens and spoilage bacteria. Plants have historically been used in traditional medicine as sources of natural antimicrobial substances for the treatment of infectious disease. Therefore, much attention has been paid to medicinal plants as a source of alternative antimicrobial strategies. Moreover, due to the growing demand for preservative-free cosmetics, herbal extracts with antimicrobial activity have recently been used in the cosmetic industry to reduce the risk of allergies connected to the presence of methylparabens. Some species belonging to the genus Cinnamomum, commonly used as spices, contain many antibacterial compounds. This paper reviews the literature published over the last five years regarding the antibacterial effects of cinnamon. In addition, a brief summary of the history, traditional uses, phytochemical constituents, and clinical impact of cinnamon is provided.     

Erythrocytic phosphatidylserine exposure and hemostatic alterations in β-thalassemia intermediate patients

Introduction

Hypercoagulable state is one of the common findings in beta-thalassemia intermedia (β-TI), particularly in splenectomized patients, with infrequent blood transfusion. Abnormality of the red blood cells (RBC) membrane due to oxidative damage is suggestive of possible etiologies. Membrane lipid peroxidation increases the exposure of phosphatidylserine (PS) that plays a role in the activation of coagulation factors V and X, subsequently initiating thrombosis. Our aim of this study was to find the probable correlation of the alteration of the PS on the RBC outer membrane with the hypercoagulable state in the β-TI patients.

Materials and methods

Our cross-sectional study was conducted on 39 splenectomized β-TI patients and 38 age-matched healthy controls. The mean age was 37 years. Analysis of the PS exposure on the RBCs was performed by fluorescein isothiocyanate (FITC) conjugated AV protein .Measurement of the coagulation factors X, V and antithrombin III (AT-III) was performed. We also checked the D-dimer levels .Analysis was performed by SPSS16.

Results

Fluorescence of FITC-Annexin V labeling on patients RBCs were higher than healthy controls; (2.8 ± 2.2%) of the patients versus (0.4 ± 0.18%) in the control group and was statistically significant (P < 0.05). Mean levels of factor X and AT-III of the patients as compared with the control group decreased and showed significant difference (P < 0.05).

Conclusions

Circulation of thalassemic RBCs, which abnormally possess PS on RBC membrane outer surface, suggests the possibility of the gradual consumption of the coagulation factors in the presence of a chronic coagulability state.     

Detection of vertical root fractures using digitally enhanced images: reverse‐contrast and colorization

Abstract – Root fracture diagnosis is a clinical difficulty that in most cases can only be detected through radiography. The objective of this study was to compare the diagnostic accuracy of two types of digitally enhanced images (reverse‐contrast and colorization) with original digital radiographies in detecting experimental root fractures. Two hundred extracted single‐rooted human teeth were endodontically instrumented and then divided in two groups, one control group and one test group, including fractured teeth. Vertical root fractures were experimentally made in the fractured group. The digital image of each tooth was taken, using the paralleling technique. There were three groups of images: (i) original, (ii) reverse contrast, and (iii) colorized. Three experienced dental specialists examined the images with no prior knowledge of the distribution of the root fractures. Two‐way analysis of variance was used to assess the differences in accuracy, sensitivity, and specificity of each technique in detecting root fractures. Cohen’s kappa coefficients were calculated to investigate the degree of interobserver agreement. The accuracy, sensitivity, and specificity of original images were 67.4%, 66.7%, and 68%, respectively; these amounts were 61.5%, 61%, and 65.5% in reverse contrast images and 66.4%, 70.7%, and 62% in colorized digital radiography. The original images had the best inter observer kappa coefficients (between 0.45 and 0.55). The results showed that the accuracy of original images is better than reverse contrast and colorized images. Use of reverse‐contrast and colorization digital images in root fracture detection should be regarded as an adjunct to other diagnostic methods not as a highly critical diagnostic aid.     

An open-label phase 1 clinical trial of the allogeneic side population adipose-derived mesenchymal stem cells in SMA type 1 patients

Neurological Sciences - Spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disorder of alpha motor neurons of spinal cord associated with progressive muscle weakness and...