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排序方式: 共有312条查询结果,搜索用时 15 毫秒
91.
Stitelman OM Wester CW De Gruttola V van der Laan MJ 《The international journal of biostatistics》2011,7(1):19
The Cox proportional hazards model or its discrete time analogue, the logistic failure time model, posit highly restrictive parametric models and attempt to estimate parameters which are specific to the model proposed. These methods are typically implemented when assessing effect modification in survival analyses despite their flaws. The targeted maximum likelihood estimation (TMLE) methodology is more robust than the methods typically implemented and allows practitioners to estimate parameters that directly answer the question of interest. TMLE will be used in this paper to estimate two newly proposed parameters of interest that quantify effect modification in the time to event setting. These methods are then applied to the Tshepo study to assess if either gender or baseline CD4 level modify the effect of two cART therapies of interest, efavirenz (EFV) and nevirapine (NVP), on the progression of HIV. The results show that women tend to have more favorable outcomes using EFV while males tend to have more favorable outcomes with NVP. Furthermore, EFV tends to be favorable compared to NVP for individuals at high CD4 levels. 相似文献
92.
von der Malsburg K Müller JM Bohnert M Oeljeklaus S Kwiatkowska P Becker T Loniewska-Lwowska A Wiese S Rao S Milenkovic D Hutu DP Zerbes RM Schulze-Specking A Meyer HE Martinou JC Rospert S Rehling P Meisinger C Veenhuis M Warscheid B van der Klei IJ Pfanner N Chacinska A van der Laan M 《Developmental cell》2011,21(4):694-707
The mitochondrial inner membrane consists of two domains, inner boundary membrane and cristae membrane that are connected by crista junctions. Mitofilin/Fcj1 was reported to be involved in formation of crista junctions, however, different views exist on its function and possible partner proteins. We report that mitofilin plays a dual role. Mitofilin is part of a large inner membrane complex, and we identify five partner proteins as constituents of the mitochondrial inner membrane organizing system (MINOS) that is required for keeping cristae membranes connected to the inner boundary membrane. Additionally, mitofilin is coupled to the outer membrane and promotes protein import via the mitochondrial intermembrane space assembly pathway. Our findings indicate that mitofilin is a central component?of MINOS and functions as a multifunctional regulator of mitochondrial architecture and protein biogenesis. 相似文献
93.
Elsenoor J. Klaver Loes M. Kuijk Lisa C. Laan Helene Kringel Sandra J. van Vliet Gerd Bouma Richard D. Cummings Georg Kraal Irma van Die 《International journal for parasitology》2013,43(3-4):191-200
Human monocyte-derived dendritic cells (DCs) show remarkable phenotypic changes upon direct contact with soluble products (SPs) of Trichuris suis, a pig whipworm that is experimentally used in therapies to ameliorate inflammation in patients with Crohn’s disease and multiple sclerosis. These changes may contribute to the observed induction of a T helper 2 (Th2) response and the suppression of Toll-like receptor (TLR)-induced Th1 and Th17 responses by human DCs primed with T. suis SPs. Here it is demonstrated that glycans of T. suis SPs contribute significantly to the suppression of the lipopolysaccharide (LPS)-induced expression in DCs of a broad variety of cytokines and chemokines, including important pro-inflammatory mediators such as TNF-α, IL-6, IL-12, lymphotoxin α (LTA), C-C Motif Ligand (CCL)2, C-X-C Motif Ligands (CXCL)9 and CXCL10. In addition, the data show that human DCs strongly bind T. suis SP-glycans via the C-type lectin receptors (CLRs) mannose receptor (MR) and DC-specific ICAM-3-grabbing non-integrin (DC-SIGN). The interaction of DCs with T. suis glycans likely involves mannose-type glycans, rather than fucosylated glycans, which differs from DC binding to soluble egg antigens of the human worm parasite, Schistosoma mansoni. In addition, macrophage galactose-type lectin (MGL) recognises T. suis SPs, which may contribute to the interaction with immature DCs or other MGL-expressing immune cells such as macrophages. The interaction of T. suis glycans with CLRs of human DCs may be essential for the ability of T. suis to suppress a pro-inflammatory phenotype of human DCs. The finding that the T. suis-induced modulation of human DC function is glycan-mediated is novel and indicates that helminth glycans contribute to the dampening of inflammation in a wide range of human inflammatory diseases. 相似文献
94.
Stroud DA Oeljeklaus S Wiese S Bohnert M Lewandrowski U Sickmann A Guiard B van der Laan M Warscheid B Wiedemann N 《Journal of molecular biology》2011,413(4):743-750
Eukaryotic cells contain multiple organelles, which are functionally and structurally interconnected. The endoplasmic reticulum-mitochondria encounter structure (ERMES) forms a junction between mitochondria and the endoplasmic reticulum (ER). Four ERMES proteins are known in yeast, the ER-anchored protein Mmm1 and three mitochondria-associated proteins, Mdm10, Mdm12 and Mdm34, with functions related to mitochondrial morphology and protein biogenesis. We mapped the glycosylation sites of ERMES and demonstrate that three asparagine residues in the N?terminal domain of Mmm1 are glycosylated. While the glycosylation is dispensable, the cytosolic C?terminal domain of Mmm1 that connects to the Mdm proteins is required for Mmm1 function. To analyze the composition of ERMES, we determined the subunits by quantitative mass spectrometry. We identified the calcium-binding GTPase Gem1 as a new ERMES subunit, revealing that ERMES is composed of five genuine subunits. Taken together, ERMES represents a platform that integrates components with functions in formation of ER-mitochondria junctions, maintenance of mitochondrial morphology, protein biogenesis and calcium binding. 相似文献
95.
Sorting switch of mitochondrial presequence translocase involves coupling of motor module to respiratory chain 总被引:4,自引:1,他引:3
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Wiedemann N van der Laan M Hutu DP Rehling P Pfanner N 《The Journal of cell biology》2007,179(6):1115-1122
The mitochondrial presequence translocase transports preproteins to either matrix or inner membrane. Two different translocase forms have been identified: the matrix transport form, which binds the heat-shock protein 70 (Hsp70) motor, and the inner membrane–sorting form, which lacks the motor but contains translocase of inner mitochondrial membrane 21 (Tim21). The sorting form interacts with the respiratory chain in a Tim21-dependent manner. It is unknown whether the respiratory chain–bound translocase transports preproteins and how the switch between sorting form and motor form occurs. We report that the respiratory chain–bound translocase contains preproteins in transit and, surprisingly, not only sorted but also matrix-targeted preproteins. Presequence translocase-associated motor (Pam) 16 and 18, two regulatory components of the six-subunit motor, interact with the respiratory chain independently of Tim21. Thus, the respiratory chain–bound presequence translocase is not only active in preprotein sorting to the inner membrane but also in an early stage of matrix translocation. The motor does not assemble en bloc with the translocase but apparently in a step-wise manner with the Pam16/18 module before the Hsp70 core. 相似文献
96.
Allosuppressive donor CD4+CD25+ regulatory T cells detach from the graft and circulate in recipients after liver transplantation 总被引:4,自引:0,他引:4
Demirkiran A Bosma BM Kok A Baan CC Metselaar HJ Ijzermans JN Tilanus HW Kwekkeboom J van der Laan LJ 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(10):6066-6072
Organ transplantation (Tx) results in a transfer of donor leukocytes from the graft to the recipient, which can lead to chimerism and may promote tolerance. It remains unclear whether this tolerance involves donor-derived regulatory T cells (Tregs). In this study, we examined the presence and allosuppressive activity of CD4+CD25+Foxp3+ Tregs in perfusates of human liver grafts and monitored the cells presence in the circulation of recipients after liver Tx. Vascular perfusions of 22 liver grafts were performed with University of Wisconsin preservation and albumin solutions. Flow cytometric analysis revealed that perfusate T cells had high LFA-1 integrin expression and had a reversed CD4 to CD8 ratio compared with control blood of healthy individuals. These findings indicate that perfusate cells are of liver origin and not derived from residual donor blood. Further characterization of perfusate mononuclear cells showed an increased proportion of CD4+CD25+CTLA4+ T cells compared with healthy control blood. Increased percentages of Foxp3+ cells, which were negative for CD127, confirmed the enrichment of Tregs in perfusates. In MLR, CD4+CD25+ T cells from perfusates suppressed proliferation and IFN-gamma production of donor and recipient T cells. In vivo within the first weeks after Tx, up to 5% of CD4+CD25+CTLA4+ T cells in recipient blood were derived from the donor liver. In conclusion, a substantial number of donor Tregs detach from the liver graft during perfusion and continue to migrate into the recipient after Tx. These donor Tregs suppress the direct pathway alloresponses and may in vivo contribute to chimerism-associated tolerance early after liver Tx. 相似文献
97.
Mitra Almasian Leah S. Wilk Paul R. Bloemen Ton G van Leeuwen Mark ter Laan Maurice C. G. Aalders 《Journal of biophotonics》2019,12(10)
This study investigates the feasibility of in vivo quantitative optical coherence tomography (OCT) of human brain tissue during glioma resection surgery in six patients. High‐resolution detection of glioma tissue may allow precise and thorough tumor resection while preserving functional brain areas, and improving overall survival. In this study, in vivo 3D OCT datasets were collected during standard surgical procedure, before and after partial resection of the tumor, both from glioma tissue and normal parenchyma. Subsequently, the attenuation coefficient was extracted from the OCT datasets using an automated and validated algorithm. The cortical measurements yield a mean attenuation coefficient of 3.8 ± 1.2 mm?1 for normal brain tissue and 3.6 ± 1.1 mm?1 for glioma tissue. The subcortical measurements yield a mean attenuation coefficient of 5.7 ± 2.1 and 4.5 ± 1.6 mm?1 for, respectively, normal brain tissue and glioma. Although the results are inconclusive with respect to trends in attenuation coefficient between normal and glioma tissue due to the small sample size, the results are in the range of previously reported values. Therefore, we conclude that the proposed method for quantitative in vivo OCT of human brain tissue is feasible during glioma resection surgery. 相似文献
98.
99.
The macrophage receptor MARCO 总被引:4,自引:0,他引:4
Kraal G van der Laan LJ Elomaa O Tryggvason K 《Microbes and infection / Institut Pasteur》2000,2(3):313-316
MARCO (macrophage receptor with collagenous structure) belongs to the class A scavenger receptor molecules. The structure and function of the molecule is described. Although it is expressed on subsets of macrophages, it can be upregulated on other macrophages after bacterial infection. The strategic position of MARCO-expressing cells in lymphoid organs suggests an important role for this bacteria-binding molecule in removal of pathogens. 相似文献
100.
Kim Wopken Hendrik P. Bijl Arjen van der Schaaf Miranda E. Christianen Olga Chouvalova Sjoukje F. Oosting Bernard F. A. M. van der Laan Jan L. N. Roodenburg C. René Leemans Ben J. Slotman Patricia Doornaert Roel J. H. M. Steenbakkers Irma M. Verdonck-de Leeuw Johannes A. Langendijk 《PloS one》2014,9(4)