Calcium Signaling Controls Pathogenic Th17 Cell-Mediated Inflammation by Regulating Mitochondrial Function

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ATM-deficient human fibroblast cells are resistant to low levels of DNA double-strand break induced apoptosis and subsequently undergo drug-induced premature senescence

DNA DSBs are induced by IR or radiomimetic drugs such as doxorubicin. It has been indicated that cells from ataxia-telangiectasia patients are highly sensitive to radiation due to defects in DNA repair, but whether they have impairment in apoptosis has not been fully elucidated. A-T cells showed increased sensitivity to high levels of DNA damage, however, they were more resistant to low doses. Normal cells treated with combination of KU55933, a specific ATM kinase inhibitor, and doxorubicin showed increased resistance as they do in a similar manner to A-T cells. A-T cells have higher viability but more DNA breaks, in addition, the activations of p53 and apoptotic proteins (Bax and caspase-3) were deficient, but Akt expression was enhanced. A-T cells subsequently underwent premature senescence after treatment with a low dose of doxorubicin, which was confirmed by G2 accumulation, senescent morphology, and SA-β-gal positive until 15 days repair incubation. Finally, A-T cells are radio-resistant at low doses due to its defectiveness in detecting DNA damage and apoptosis, but the accumulation of DNA damage leads cells to premature senescence.     

Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation

The structure of the I domain of integrin alpha L beta 2 bound to the Ig superfamily ligand ICAM-1 reveals the open ligand binding conformation and the first example of an integrin-IgSF interface. The I domain Mg2+ directly coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue Glu-241 enables a critical salt bridge. Liganded and unliganded structures for both high- and intermediate-affinity mutant I domains reveal that ligand binding can induce conformational change in the alpha L I domain and that allosteric signals can convert the closed conformation to intermediate or open conformations without ligand binding. Pulling down on the C-terminal alpha 7 helix with introduced disulfide bonds ratchets the beta 6-alpha 7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity.     

Immunohistochemical localization of type II and type I collagens in articular cartilage of the femoral head of dexamethasone-treated rats

The immunohistochemical localization of type II and type I collagens was examined in the articular cartilage of the femoral head of growing rats injected systemically with 5 mg kg−1 dexamethasone for 2 weeks every other day. The intensities of immunostaining for type II collagen, measured by microphotometry, was highest in the flattened cell layer and high in the hypertrophic cell layer, moderate in the proliferative cell and transitional cell layers and low in the superficial layer. After dexamethasone administration, the intensities decreased markedly in the flattened cell layer and slightly in the hypertrophic cell layer, although the decreases in other layers were negligible. The staining intensities for type I collagen were highest in the flattened cell layer, low in the superficial and transitional cell layers and very low in the proliferative and hypertrophic cell layers. After dexamethasone administration, the intensities increased markedly in the flattened cell layer and slightly in the superficial and proliferative cell layers, but did not change in the transitional and hypertrophic cell layers. Thus, dexamethasone administration caused a decrease in type II collagen and an increase in type I collagen in the matrix of the surface portion of articular cartilage. The composition of isoforms of collagen in the matrix changed after the steroid administration. The results strongly suggest that the shift in collagen composition from type II to type I predominance is a cause of the degeneration of the articular cartilage after glucocorticoid administration. This revised version was published online in November 2006 with corrections to the Cover Date.     

Movement of outbreak populations of mountain pine beetle: influences of spatiotemporal patterns and climate

Insect outbreaks exert landscape-level influences, yet quantifying the relative contributions of various exogenous and endogenous factors that contribute to their pattern and spread remains elusive. We examine an outbreak of mountain pine beetle covering an 800 thousand ha area on the Chilcotin Plateau of British Columbia, Canada, during the 1970s and early 1980s. We present a model that incorporates the spatial and temporal arrangements of outbreaking insect populations, as well as various climatic factors that influence insect development. Onsets of eruptions of mountain pine beetle demonstrated landscape-level synchrony. On average, the presence of outbreaking populations was highly correlated with outbreaking populations within the nearest 18  km the same year and local populations within 6 km in the previous two years. After incorporating these spatial and temporal dependencies, we found that increasing temperatures contributed to explaining outbreak probabilities during this 15  yr outbreak. During collapse years, landscape-level synchrony declined while local synchrony values remained high, suggesting that in some areas host depletion was contributing to population decline. Model forecasts of outbreak propensity one year in advance at a 12 by 12  km scale provided 80% accuracy over the landscape, and never underestimated the occurrence of locally outbreaking populations. This model provides a flexible approach for linking temperature and insect population dynamics to spatial spread, and complements existing decision support tools for resource managers.     

The Potential Value of Preoperative MRI Texture and Shape Analysis in Grading Meningiomas: A Preliminary Investigation

OBJECT: Preoperative knowledge of meningioma grade is essential for planning treatment and surgery. The purpose of this study was to investigate the diagnostic value of MRI texture and shape analysis in grading meningiomas. METHODS: A surgical database was reviewed to identify meningioma patients who had undergone tumor resection between January 2015 and December 2016. Preoperative MR images were retrieved and analyzed. Texture and shape analysis was conducted to quantitatively evaluate tumor heterogeneity and morphology. Three machine learning classifiers were trained with these features to build classification models. The performance of the features and classification models was assessed. RESULTS: A total of 131 patients were included in this study: 21 with high-grade meningiomas and 110 with low-grade meningiomas. Three texture features were selected: Horzl_RLNonUni, S(2,2)SumOfSqs, and WavEnHL_s-3; three shape features were selected: GeoFv, GeoW4, and GeoW5b. The Mann–Whitney test indicated that all six features were significantly different between high-grade and low-grade meningiomas. AUC values were generally greater than 0.50 (range, 0.73 to 0.88). Sensitivities and specificities ranged from 47.62% to 90.48% and 69.09% to 96.36%, respectively. Among the nine classification models obtained, the one built by training the SVM classifier with all six features achieved the best performance, with a sensitivity, specificity, diagnostic accuracy, and AUC of 0.86, 0.87, 0.87, and 0.87, respectively. CONCLUSIONS: Texture and shape analysis, especially when combined with a SVM classifier, can provide satisfactory performance in the preoperative determination of meningioma grade and is thus potentially useful for clinical application.     

^18F标记表皮生长因子受体酪氨酸激酶抑制剂4-苯氨基-喹唑啉类方法进展

分子成像可在活体状态下直观判断分子靶向药物靶位点存在状态,分子靶向药物与靶位点结合率及精确监测分子靶向药物的治疗疗效,为临床治疗方案的选择和调整提供依据。EGFR是多种恶性肿瘤的关键靶点。研究表明放射性核素标记的表皮生长因子酪氨酸激酶抑制剂是很有潜力的成像探针,其中尤以4-苯氨基．喹唑啉类研究最为广泛。本文简要介绍4-苯氨基-喹唑啉不同衍生物的结构及性质。阐述了^18F标记4-苯氨基．喹唑啉类的主要方法：先用^18F标记苯氨基,然后将^18F标记化合物与喹唑啉或衍生物进行连接,和^18F标记喹唑啉或其衍生物,然后与苯胺或其衍生物进行连接。并且进一步比较不同示踪剂在体外、动物和人体内生物分布、肿瘤摄取和代谢的异同。特别是对^18F标记示踪剂与11c标记示踪剂在动物和人体分布进行比较。尤其是[^18F]ML04肝脏摄取低,肿瘤．本底高,多数学者认为[^18F]ML04是最有潜力成为^18F标记表皮生长因子受体酪氨酸激酶抑制剂4-苯氨基-喹唑啉类示踪剂。     

我国生物丁醇分离提取技术研究进展

本文概述了目前国内外生物丁醇生产体系中的分离提取技术,包括液液萃取、气提、吸附、精馏和渗透汽化技术等的应用研究现状,详细阐述了上述几种方法在分离提取生物丁醇方面的优势与不足,对各类方法的分离特性和效果进行了比较,并展望了生物丁醇分离提取技术的发展前景。