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Background Neural crest defects lead to congenital heart disease involving outflow tract malformation. Integrin-linked-Kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in neural crest, but its role in neural crest and outflow tract morphogenesis remains unknown. Results We ablated ILK specifically in neural crest by Wnt1-Cre. ILK ablation resulted in abnormal migration and overpopulation of neural crest cells in the pharyngeal arches and outflow tract and a significant reduction in the expression of Ncam and extracellular matrix components. ILK mutant embryos exhibited an enlarged common arterial trunk and ventricular septal defect. Reduced smooth muscle differentiation, but increased ossification and neurogenesis/innervation were observed in ILK mutant outflow tract that may partly be due to reduced TGFß2 but increased BMP signaling. Consistent with these observations, microarray analysis of FACS sorted neural crest cells revealed reduced expression of genes associated with muscle differentiation, but increased expression of genes of neurogenesis and osteogenesis. Conclusions Our results demonstrate that ILK plays essential roles in neural crest and outflow tract development by mediating complex crosstalk between cell-matrix and multiple signaling pathways. Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants. [ABSTRACT FROM AUTHOR]

Not uncommonly, differentiating multiple sclerosis (MS) from ischemic cerebral vascular disease is difficult based on conventional magnetic resonance imaging (MRI). We aim to determine whether preferential occult injury in the normal-appearing corpus callosum (NACC) is more severe in patients with MS than symptomatic carotid occlusion by comparing fractional anisotropy (FA) from diffusion tensor imaging (DTI). Eighteen patients (eight men, ten women; mean age, 38.6 years) with MS and 32 patients (24 men, eight women; mean age, 64.0 years) with symptomatic unilateral internal carotid occlusion were included. DTI (1.5 T) were performed at corpus callosum which were normal-appearing on fluid-attenuated inversion recovery MRI. Mean FA was obtained from the genu, anterior body, posterior body, and splenium of NACC. Independent-sample t test statistical analysis was performed. The FA values in various regions of NACC were lower in the MS patients than symptomatic carotid occlusion patients, which was statistically different at the anterior body (0.67 ± 0.12 vs 0.74 ± 0.06, P = 0.009), but not at genu, posterior body, and splenium (0.63 ± 0.09 vs 0.67 ± 0.07, P = 0.13; 0.68 ± 0.09 vs 0.73 ± 0.05, P = 0.07; 0.72 ± 0.09 vs 0.76 ± 0.05, P = 0.13). MS patients have lower FA in the anterior body of NACC compared to patients with symptomatic carotid occlusion. It suggests that DTI has potential ability to differentiate these two conditions due to the more severe preferential occult injury at the anterior body of NACC in MS. [ABSTRACT FROM AUTHOR]

The Brillouin equations with strong nonlinearity are solved using a perturbation technique. The calculated results agree quite well with the published experimental results [1, 2]. In addition some new conclusions are obtained from our analysis. [ABSTRACT FROM AUTHOR]

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 g/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 g/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways. [ABSTRACT FROM AUTHOR]

Cyclin E1 regulates the initiation of S-phase in cellular division. However, in many cancers, cyclin E1 is aberrantly overexpressed and this molecular phenotype correlates with increased tumor aggressiveness and poor patient survival. The molecular cause(s) of cyclin E1 abnormalities in cancers is poorly understood. Here, we show that cyclin E1 overexpression in cancer is promoted by dysregulation of the protein phosphatase PP2A-B55β. PP2A-B55β targets the N- and C-terminal phosphodegrons of cyclin E1 for dephosphorylation, thus protecting it from degradation mediated by the SCFFbxw7 ubiquitin ligase. Augmented B55b expression stabilizes cyclin E1 and promotes its overexpression in cancer-derived cell lines and breast tumors. Conversely, B55β ablation enforces the degradation of cyclin E1 and inhibits cancer cell proliferation in vitro and tumor formation in vivo. Therefore, PP2A-B55β promotes cyclin E1 overexpression by antagonizing its degradation and its inhibition could represent a therapeutic mechanism for abrogating cyclin E1 function in cancers. [ABSTRACT FROM AUTHOR]