排序方式: 共有26条查询结果,搜索用时 31 毫秒
1.
Katrin Trummal Külli T?nism?gi Ene Siigur Anu Aasp?llu Annika Lopp Tarvo Sillat Riste Saat Lagle Kasak Indrek Tammiste Priit Kogerman Nisse Kalkkinen Jüri Siigur 《Toxicon》2005,46(1):46-61
A novel endothelial cell apoptosis inducing metalloprotease (VLAIP) was found in the snake venom of Vipera lebetina. This metalloprotease is a heterodimeric glycoprotein with molecular mass of about 106 kDa. The protease hydrolyzes azocasein, fibrinogen and oxidized insulin B-chain. The enzyme readily hydrolyzes the Aalpha-chain and more slowly Bbeta-chain of fibrinogen. VLAIP does not cleave fibrin. The complete amino acid sequences of the two different monomers of VLAIP are deduced from the nucleotide sequences of cDNAs encoding these proteins. The full-length cDNA sequences of the VLAIP-A and VLAIP-B encode open reading frames of 616 and 614 amino acids that include signal peptide, propeptide and mature metalloproteinase with disintegrin-like and cysteine-rich domains. VLAIP belongs to the metalloprotease/disintegrin family of reprolysins and has high identity with the proteins that induce apoptosis of endothelial cells. Treatment of HUVEC cells with VLAIP induces changes in the attachment of cells to the substrate and causes cell death. We demonstrated that VLAIP inhibits endothelial cell adhesion to extracellular matrix proteins: fibrinogen, fibronectin, vitronectin, collagen I, and collagen IV. The induction of apoptosis by VLAIP was shown by means of a typical DNA fragmentation pattern of apoptotic cells as well as by monitoring phosphatidylserine externalization using annexin V-FITC staining and flow cytometric analysis. 相似文献
2.
CD44 is the main cellular receptor for hyaluronic acid (HA). We previously found that overexpression of CD44 inhibited tumor growth of mouse fibrosarcoma cells in mice. Here, we show that soluble recombinant CD44 HA-binding domain (CD44-HABD) acts directly onto endothelial cells by inhibiting endothelial cell proliferation in a cell-specific manner. Consequently, soluble recombinant CD44-HABD also blocked angiogenesis in vivo in chick and mouse, and thereby inhibited tumor growth of various origins at very low doses (0.25 mg/kg x day). The antiangiogenic effect of CD44 is independent of its HA-binding capacity, since mutants deficient in HA binding still maintain their antiangiogenic and antiproliferative properties. Recombinant CD44-HABD represents a novel class of angiogenesis inhibitors based on a cell-surface receptor. 相似文献
3.
Hayward C Wilson KA Lagle K Kraemer HC Killen JD Taylor CB 《Depression and anxiety》2008,25(3):200-206
To evaluate a developmental psychopathology approach for understanding adolescent social anxiety, parent-reported predictors of social anxiety were examined in a nonclinical sample of adolescents. Structured diagnostic interviews were obtained from biological parents of 770 participants. Potential risk factors assessed included child characteristics: negative affect, shyness, separation anxiety disorder, and childhood chronic illness, as well as parent characteristics: major depression, panic disorder, and agoraphobia. Adolescent social anxiety was measured multiple times during high school. Findings indicate stability in social anxiety symptoms across time. Parent-reported, childhood negative affect, shyness, and chronic illness as well as parental panic disorder or agoraphobia were associated with adolescent social anxiety. Interactions were observed between parent-reported childhood shyness and gender and between parent-reported childhood shyness and parent-reported childhood chronic illness in the prediction of social anxiety. Parent-reported childhood shyness was a stronger predictor of adolescent social anxiety in females compared to males. The combined effect of subjects being positive for both parent-reported childhood shyness and parent-reported childhood chronic illness was greater than would be expected based on additive effects. This study provides support for a multifactorial and developmentally informed understanding of adolescent social anxiety. 相似文献
4.
Nanotechnology in Glycomics: Applications in Diagnostics,Therapy, Imaging,and Separation Processes 下载免费PDF全文
Erika Dosekova Jaroslav Filip Tomas Bertok Peter Both Peter Kasak Jan Tkac 《Medicinal research reviews》2017,37(3):514-626
This review comprehensively covers the most recent achievements (from 2013) in the successful integration of nanomaterials in the field of glycomics. The first part of the paper addresses the beneficial properties of nanomaterials for the construction of biosensors, bioanalytical devices, and protocols for the detection of various analytes, including viruses and whole cells, together with their key characteristics. The second part of the review focuses on the application of nanomaterials integrated with glycans for various biomedical applications, that is, vaccines against viral and bacterial infections and cancer cells, as therapeutic agents, for in vivo imaging and nuclear magnetic resonance imaging, and for selective drug delivery. The final part of the review describes various ways in which glycan enrichment can be effectively done using nanomaterials, molecularly imprinted polymers with polymer thickness controlled at the nanoscale, with a subsequent analysis of glycans by mass spectrometry. A short section describing an active glycoprofiling by microengines (microrockets) is covered as well. 相似文献
5.
H Wolinsky S Goldfischer L Capron F Capron B Coltoff-Schiller L Kasak 《Circulation research》1978,42(6):821-831
Vascular disease in diabetics could arise in part from altered vessel wall catebolism. Specific activities of hydrolases in aortic smooth muscle cells from rats with streptozotocin-induced diabetes were measured. Enyzmes included: neutral alpha-glucosidase, alpha-mannosidase, and lysosomal N-acetyl beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 4,8, and 11 weeks of diabetes, activities of all enzymes studied were decreased significantly in diabetic vessels, decreases ranging from 15% for cathepsin C to 62% for alpha-mannosidase. After 3 weeks of diabetes, insulin treatment for 1 week restored enzyme levels to normal. After 7 weeks of diabetes, 1 week of insulin treatment did not restore enzyme levels fully to normal (acid cholesteryl esterase was unchanged); 4 weeks of insulin did. Acid phosphatase and N-acetyl beta-glucosaminidase activities were reduced markedly in histochemical studies of diabetic aortas at all time periods and were restored by insulin treatment. Alloxan-induced diabetes gave results similar to those with streptozotocin. Significant decreases of aortic hydrolase activities, including those of lysosomes, occur in experimental diabetes mellitus and could contribute to accumulation of substrates in vascular smooth muscle cells. 相似文献
6.
7.
Assessing computational predictions of the phenotypic effect of cystathionine‐beta‐synthase variants
Laura Kasak Constantina Bakolitsa Zhiqiang Hu Changhua Yu Jasper Rine Dago F. Dimster‐Denk Gaurav Pandey Greet De Baets Yana Bromberg Chen Cao Emidio Capriotti Rita Casadio Joost Van Durme Manuel Giollo Rachel Karchin Panagiotis Katsonis Emanuela Leonardi Olivier Lichtarge Pier Luigi Martelli David Masica Sean D. Mooney Ayodeji Olatubosun Predrag Radivojac Frederic Rousseau Lipika R. Pal Castrense Savojardo Joost Schymkowitz Janita Thusberg Silvio C.E. Tosatto Mauno Vihinen Jouni Vliaho Susanna Repo John Moult Steven E. Brenner Iddo Friedberg 《Human mutation》2019,40(9):1530-1545
Accurate prediction of the impact of genomic variation on phenotype is a major goal of computational biology and an important contributor to personalized medicine. Computational predictions can lead to a better understanding of the mechanisms underlying genetic diseases, including cancer, but their adoption requires thorough and unbiased assessment. Cystathionine‐beta‐synthase (CBS) is an enzyme that catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine, and in which variations are associated with human hyperhomocysteinemia and homocystinuria. We have created a computational challenge under the CAGI framework to evaluate how well different methods can predict the phenotypic effect(s) of CBS single amino acid substitutions using a blinded experimental data set. CAGI participants were asked to predict yeast growth based on the identity of the mutations. The performance of the methods was evaluated using several metrics. The CBS challenge highlighted the difficulty of predicting the phenotype of an ex vivo system in a model organism when classification models were trained on human disease data. We also discuss the variations in difficulty of prediction for known benign and deleterious variants, as well as identify methodological and experimental constraints with lessons to be learned for future challenges. 相似文献
8.
Wyatt T. Clark Laura Kasak Constantina Bakolitsa Zhiqiang Hu Gaia Andreoletti Giulia Babbi Yana Bromberg Rita Casadio Roland Dunbrack Lukas Folkman Colby T. Ford David Jones Panagiotis Katsonis Kunal Kundu Olivier Lichtarge Pier L. Martelli Sean D. Mooney Conor Nodzak Lipika R. Pal Predrag Radivojac Castrense Savojardo Xinghua Shi Yaoqi Zhou Aneeta Uppal Qifang Xu Yizhou Yin Vikas Pejaver Meng Wang Liping Wei John Moult Guoying Karen Yu Steven E. Brenner Jonathan H. LeBowitz 《Human mutation》2019,40(9):1519-1529
The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α‐N‐acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to .61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population‐scale analysis of disease epidemiology and rare variant association analysis. 相似文献
9.
Põlluste K Alop J Groene O Härm T Merisalu E Suurorg L 《Health promotion international》2007,22(4):327-336
The health-promoting hospitals (HPH) movement in Estonia was initiated in 1999. This study aimed to compare the implementation of health-promoting and quality-related activities in HPH and those which have not joined the HPH network (non-HPH). In the beginning of 2005, a postal survey was conducted among the top managers of 54 Estonian hospitals. The questionnaire was based on the WHO standards for HPH and on the set of the national quality assurance (QA) requirements for health services. The study demonstrated some significant differences in the uptake of health promotion and QA activities between HPH and non-HPH. For example, regular patient satisfaction studies were conducted in 83% of HPH and 46% of non-HPH (P < 0.03) and 65% of HPH and 46% of non-HPH cooperated with various patient organizations (P < 0.03). Systems for reporting and analysis of complications were implemented in 71% of HPH and 33% of non-HPH (P < 0.03); also, the implementation of various guidelines was more developed in HPH. All HPH have carried out a risk analysis on the workplace and staff job satisfaction studies were conducted in 89% of HPH and 41% non-HPH (P < 0.05). This study indicates that the concepts of HPH and QA are closely related. Making progress in health promotion is accompanied with QA and vice versa. Implementation of health-promoting activities in hospitals will promote the well-being and health of patients and hospital staff, and creates a supportive environment to provide safe and high-quality health services. 相似文献
10.
The depletion of fossil fuels and associated environmental problems have drawn our attention to renewable energy resources in order to meet the global energy demand. Electrocatalytic hydrogen evolution has been considered a potential energy solution due of its high energy density and environment friendly technology. Herein, we have successfully synthesized a noble-metal-free Co–Ni/MoS2 nanocomposite for enhanced electrocatalytic hydrogen evolution. The nanocomposite has been well characterized using HRTEM, elemental mapping, XRD, and XPS analysis. The as-synthesized nanocomposite exhibits a much smaller onset potential and better current density than those of Co–MoS2, Ni–MoS2 and MoS2, with a Tafel value of 49 mV dec−1, which is comparable to that of a commercial Pt/C catalyst. The synergistic effect and interfacial interaction of Co–Ni bimetallic nanoparticles enhances the intrinsic modulation in the electronic structure resulting in an improved HER performance. Moreover, the electrochemical impedance spectroscopic results suggest smaller resistance values for the Co–Ni/MoS2 nanocomposite, compared to those for the charge transfer of bare nanosheets, which increase the faradaic process and in turn enhance the HER kinetics for a better performance. Our as-synthesized Co–Ni/MoS2 nanocomposite holds great potential for the future synthesis of noble-metal-free catalysts.A noble-metal-free Co–Ni/MoS2 nanocomposite was synthesized, which showed enhanced electrocatalytic hydrogen evolution performance. 相似文献