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81.
Miriam Schmidts Valeska Frank Tobias Eisenberger Saeed al Turki Albane A. Bizet Dinu Antony Suzanne Rix Christian Decker Nadine Bachmann Martin Bald Tobias Vinke Burkhard Toenshoff Natalia Di Donato Theresa Neuhann Jane L. Hartley Eamonn R. Maher Radovan Bogdanovi Amira Peco‐Anti Christoph Mache Matthew E. Hurles Ivana Joksi Marija Gu‐eki Jelena Dobricic Mirjana Brankovic‐Magic Hanno J. Bolz Gregory J. Pazour Philip L. Beales Peter J. Scambler Sophie Saunier Hannah M. Mitchison Carsten Bergmann 《Human mutation》2013,34(5):714-724
Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib‐polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer‐Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer‐Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end‐stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono‐renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy. 相似文献
82.
Pascal Büttner Dirk Dhler Sofia Korenko Sebastian Mhrlein Sebastian Bochmann Nicolas Vogel Ignacio Mínguez-Bacho Julien Bachmann 《RSC advances》2020,10(47):28225
TiO2 nanotubes generated by anodization of metallic titanium sputter-coated on indium tin oxide (ITO) substrates are used as a conductive scaffold for all solid-state Sb2S3-sensitized extremely thin absorber (ETA) solar cells. A blocking layer of TiO2 placed between Ti and ITO in combination with optimized Ti deposition and anodization conditions enables the formation of crack-free layers of straight, cylindrical TiO2 nanotubes of tunable length and diameter. ALD (atomic layer deposition) is subsequently used to coat this substrate conformally with a highly pure Sb2S3 light absorber layer under an inert atmosphere. The high absorption coefficient of Sb2S3 as compared to molecular dyes allows for the utilization of very short nanotubes, which facilitates the infiltration of the organic hole transport material and formation of a p–i–n heterojunction in an interdigitated and tunable geometry. We investigate the influence of nanotube length and of the absorber thickness to enhance the photocurrent value to twice that of planar reference structures.TiO2 nanotubes generated by anodization of metallic titanium sputter-coated on indium tin oxide (ITO) substrates are used as a conductive scaffold for all-solid-state Sb2S3-sensitized extremely thin absorber (ETA) solar cells. 相似文献
83.
84.
Early development of human lymphomas in a prostate cancer xenograft program using triple knock‐out Immunocompromised mice 下载免费PDF全文
85.
86.
Monteiro CA Bachmann LH Desmond RA Squires KE Vermund SH Hook EW Schwebke JR Hoesley CJ 《AIDS research and human retroviruses》2004,20(6):577-583
The objectives of this study were to assess the prevalence and incidence of curable sexually transmitted infections (STI), i.e., gonorrhea, chlamydial infection, or trichomoniasis, in a cohort of HIV-infected women. The study population was derived from women seeking primary care at an outpatient university HIV clinic who were participants in a women's natural history study. Enrollees (n = 225) were predominantly African-American, heterosexually infected, with mean age 35 years. Mean entry CD4+ T cell count was 405 cells/mm3. Over 6% were STI positive at initial screening. Subsequently, the combined curable STI incidence was 4.82/1000 woman-months over a median of 33 months of observation. Of 36 incident STIs, trichomoniasis was most common (n = 32). Predictors for acquisition of a curable STI included absenteeism at scheduled clinic appointments, RR = 1.99 (1.28, 3.08), and a higher CD4+ T cell count, RR = 1.15 (1.0028, 1.3115) for 100 cells. Interventions to prevent curable STI in HIV-infected women are warranted in primary care settings. 相似文献
87.
88.
Michelle K. York Deepak K. Gupta Cassandra F. Reynolds Eric Farber-Eger Quinn S. Wells Katherine N. Bachmann Meng Xu Frank E. Harrell Thomas J. Wang 《Journal of the American College of Cardiology》2018,71(19):2079-2088
Background
Circulating B-type natriuretic peptide (BNP) concentrations strongly predict mortality in patients with heart failure (HF). Both cardiac and extracardiac stimuli influence BNP levels, suggesting that BNP might have similar prognostic value in patients without HF.Objectives
The aim of this study was to compare the prognostic value of BNP between patients with and those without HF.Methods
Using the Vanderbilt University Medical Center electronic health record, 30,487 patients (median age 63 years, 50% men, 17% black, 38% with HF) who had a first plasma BNP measurement between 2002 and 2013, with follow-up through 2015, were studied. The risk for death according to BNP level was quantified using multivariate Cox proportional hazards models.Results
BNP levels were lower in patients without HF (median 89 pg/ml; interquartile range: 34 to 238 pg/ml) compared with those with HF (median 388 pg/ml; interquartile range: 150 to 940 pg/ml) (p < 0.0001). Over 90,898 person-years of follow-up, 5,903 patients without HF (31%) and 6,181 patients with HF (53%) died. In multivariate models including demographic and clinical characteristics, BNP and age were the strongest predictors of death in both patients with and those without HF. In acute care settings and even among outpatients with modestly elevated BNP, the risk for death according to BNP was similar between patients with and those without HF. For instance, a BNP level of 400 pg/ml was associated with a 3-year risk for death of 21% (95% confidence interval: 20% to 23%) and 19% (95% confidence interval: 17% to 20%) in patients with and those without HF, respectively.Conclusions
Among patients without HF, plasma BNP level is a stronger predictor of death than traditional risk factors. The risk for death associated with any given BNP level is similar between patients with and those without HF, particularly in the acute care setting. 相似文献89.
Marcus Pohl Qixian Shan Thomas Petsch Beata Styp-Rekowska Patricia Matthey Markus Bleich Sebastian Bachmann Franziska Theilig 《Journal of the American Society of Nephrology : JASN》2015,26(6):1269-1278
Transepithelial water flow across the renal proximal tubule is mediated predominantly by aquaporin-1 (AQP1). Along this nephron segment, luminal delivery and transepithelial reabsorption are directly coupled, a phenomenon called glomerulotubular balance. We hypothesized that the surface expression of AQP1 is regulated by fluid shear stress, contributing to this effect. Consistent with this finding, we found that the abundance of AQP1 in brush border apical and basolateral membranes was augmented >2-fold by increasing luminal perfusion rates in isolated, microperfused proximal tubules for 15 minutes. Mouse kidneys with diminished endocytosis caused by a conditional deletion of megalin or the chloride channel ClC-5 had constitutively enhanced AQP1 abundance in the proximal tubule brush border membrane. In AQP1-transfected, cultured proximal tubule cells, fluid shear stress or the addition of cyclic nucleotides enhanced AQP1 surface expression and concomitantly diminished its ubiquitination. These effects were also associated with an elevated osmotic water permeability. In sum, we have shown that luminal surface expression of AQP1 in the proximal tubule brush border membrane is regulated in response to flow. Cellular trafficking, endocytosis, an intact endosomal compartment, and controlled protein stability are the likely prerequisites for AQP1 activation by enhanced tubular fluid shear stress, serving to maintain glomerulotubular balance. 相似文献
90.
Dexamethasone resistance in B-cell precursor childhood acute lymphoblastic leukemia occurs downstream of ligand-induced nuclear translocation of the glucocorticoid receptor 总被引:6,自引:1,他引:6 下载免费PDF全文
Glucocorticoids are among the most effective agents used in the treatment of childhood acute lymphoblastic leukemia (ALL), and patient response to treatment is an important determinant of long-term outcome. Despite its clinical significance, the molecular basis of glucocorticoid resistance in lymphoid malignancies is still poorly understood. We have recently developed a highly clinically relevant experimental model of childhood ALL, in which primary childhood ALL biopsies were established as xenografts in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. The in vivo and in vitro responses of a panel of these xenografts to the glucocorticoid, dexamethasone, reflected the outcome of the patients from whom they were derived. In this report we show that glucocorticoid resistance in B-cell precursor (BCP) ALL xenografts was not due to down-regulation of the glucocorticoid receptor (GR) nor to defective ligand binding of the GR. Moreover, dexamethasone-induced GR translocation from the cytoplasm to the nucleus was comparable in all xenografts. However, glucocorticoid resistance was associated with profoundly attenuated induction of the BH3-only proapoptotic protein, Bim, when xenograft cells were exposed to dexamethasone. These results show that dexamethasone resistance in BCP ALL xenografts occurs downstream of ligand-induced nuclear translocation of the GR, but upstream of Bim induction. 相似文献