ABSTRACT
In this research, we studied the formation of Drosophila melanogaster FADD (Fas-associated death domain-containing protein) amyloid fiber and its influence on signal transduction in IMD (Immune deficiency) signaling pathway to better understand the regulation mechanism of Drosophila innate immune signaling pathway, which will provide reference for the immune regulation in other species. First, we purified dFADD protein expressed in Escherichia coli and performed Sulfur flavin T binding and transmission electron microscopy to identify the dFADD amyloid fibers formed in vitro. Then we investigated the formation of dFADD polymers in S2 cells using SDD-AGE and confocal microscope. We also constructed dFADD mutants to find out which domain is essential to fiber formation and its effect on IMD signal transduction. Our results revealed that dFADD could be polymerized to form amyloid fiber polymers in vitro and inside the cells. Formation of fibers relies on DED (Death-effector domain) domain of dFADD, since DED domain-deleted mutant existed as a monomer. Dual luciferase reporter assay showed that intact DED domain was required for the induction of downstream antimicrobial peptides, indicating that fiber formation was the key to IMD signal transduction. Our study revealed the role of dFADD in mediating the cascade between IMD and Dredd in the IMD signaling pathway by forming amyloid fibers, suggesting an evolutionarily conserved regulatory mechanism of innate immune signaling pathway.
Subject(s)
Animals , Drosophila Proteins , Allergy and Immunology , Drosophila melanogaster , Allergy and Immunology , Fas-Associated Death Domain Protein , Allergy and Immunology , Immunity, Innate , Allergy and Immunology , Signal TransductionABSTRACT
Objective To investigate the feasibility of the highGresolution MRI (HRGMRI)in diagnosing the intracranial artery dissection (IAD)and to improve radiological diagnostic accuracy in clinical practice.Methods The clinical data and imaging data of 43 patients with suspected IAD were analyzed retrospectively.HRGMRI and DSA examinations were performed.HRGMRI images were reviewed by two experienced radiologists independently,and DSA images were analyzed by a neurosurgeon.FollowGup durations were from 3 months up to 12 months,and then the clinical diagnoses of IAD were made.The sensitivity,specificity,positive predictive value (PPV),and negative predictive value (NPV)of HRGMRI were calculated,and the consistency of HRGMRI and DSA in the diagnosis of IAD was made.Results 32 over 43 patients were detected to be positive by HRGMRI,however,34 of 43 patients were diagnosed as IAD clinically.The sensitivity and specificity of HRGMRI for detecting IAD were 9 1.2% and 88.9%,respectively.The PPV was 96.9%,and the NPV was 72.7%.For DSA,30 patients with IAD were detected and 1 3 patients had negative results.Compared with the HRGMRI (3 2/43),the coincidence rate of two examinations was 86.0%.McNemer test (P＝0.687)indicated that there was no significant difference between two methods.Conclusion HRGMRI has excellent soft tissue contrast and spatial resolution.As a nonGinvasive modality with good tissue contrast and spatial resolution,it plays an important role in the diagnosis,differential diagnosis and followGup of IAD.
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Objective To investigate CT and MRI findings of primary malignant fibrous histiocytoma (MFH)in the kidney. Methods The clinical data and imaging findings of 7 patients with primary renal MFH proved by histopathology were reviewed retrospectively.Results Tumors were unilateral in all patients,in which 5 cases were in the left kidney and 2 cases in the right kidney.The maximum diameter of the lesions ranged from 3.5 to 17.1 cm,with a mean of (8.7±3.9)cm.All the masses showed shallow lobulated or oval, with obscure boundary.On CT plain scan,heterogeneous isodensity/hypodensity were showed in 7 cases,necrosis occured in 7 cases, intratumoral hemorrhage in 2 cases and calcification in 3 cases.MRI also showed heterogeneous signal intensity.No obvious pseudocapsule was found in 6 cases.On dynamic contrast enhancement scan mild-moderate progressive enhancement was showed in corticomedullary and parenchymal phase in all 7 cases.In delay phase slightly decreased enhancement were showed in 5 cases,and similar or slightly higher enhancement corresponding to the parenchymal phase was showed in 2 cases.However,lower enhancement was showed in the tumors on all 3 phases than that in the renal cortex.Besides,the tumors invaded the renal vein (n=1)and the adjacent structure (n=3).Conclusion No specific imaging findings of primary renal MFH are found.The dynamic contrast enhancement might be helpful for its diagnosis to some extent,and clinical data should be integrated with imaging findings together to differentiate renal MFH from other renal neoplasms.The final diagnosis relies on pathology and immunohistochemistry examination.
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Objective To analyze the topological characteristics of the brain structural network in primary angle-closure glaucoma (PACG) patients by applying graph theoretical approaches.Methods From October 2015 to April 2017, nineteen PACG patients and nineteen gender-and age-matched healthy controls (HCs) were enrolled to undergo MRI scan. The whole brain was parceled into 90 regions by automated anatomical labeling template, and the brain structural network was constructed by the fiber distribution of continuous tracking method.Both the weighted and unweighted network analyses were performed.The global and regional properties were computed by graph theoretical analysis.To compare the brain network regional properties between two groups, two-sample t-test was utilized.The correlations between the brain structural network properties and clinical parameters were further analysed. Results Both two groups were found to follow the efficient small-world characteristics. Compared to HCs, the brain structural network in PACG patients showed no statistical significance in the small-worldness, average shortest path, clustering coefficient, global efficiency and local efficiency(P＞0.05). Compared to the HCs, the PACG patients showed decreased nodal efficiency in the right superior frontal gyrus, right inferior frontal gyrus, left median cingulate and paracingulate gyri, left amygdala and left cuneus(P＜0.05). Compared to HCs, the PACG patients showed decreased node degree in left superior frontal gyrus, medial orbital, right inferior frontal gyrus, left amygdala, left cuneus and left lingual gyrus(P＜0.05). Compared with the hub regions in healthy controls'network, we found that two hub regions disappeared.Those hubs were right inferior parietal lobule and left middle temporal gyrus. Node degree in left amygdala showed negatively correlated with visual ability (r=-0.679, P=0.001). Node degree in left lingual gyrus showed negatively correlated with vertical CDR(r=-0.791, P=0.001),which showed positively correlated with visual acuity(r=0.538, P=0.018).Conclusions The brain structural network in PACG patients showed small-worldness properties as HCs group. The alterations of local properties in visual, emotion-cognition brain regions were observed, manifesting that PACG can affect the topology properties of the structural brain network.