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31.
João Paulo Oliveira Corrêa Camilo Elber Vital Marcos Vinícius Marques Pinheiro Diego Silva Batista Cleber Witt Saldanha Ana Cláudia Ferreira da Cruz Marcela Morato Notini Débora Márcia Silva Freitas Fábio Murilo DaMatta Wagner Campos Otoni 《In vitro cellular & developmental biology. Plant》2016,52(1):45-55
32.
Maria Troullinaki Vasileia‐Ismini Alexaki Ioannis Mitroulis Anke Witt Anne Klotzschevon Ameln Kyoung‐Jin Chung Triantafyllos Chavakis Matina Economopoulou 《Journal of cellular and molecular medicine》2019,23(4):2362-2371
The mechanism underlying vasoproliferative retinopathies like retinopathy of prematurity (ROP) is hypoxia‐triggered neovascularisation. Nerve growth factor (NGF), a neurotrophin supporting survival and differentiation of neuronal cells may also regulate endothelial cell functions. Here we studied the role of NGF in pathological retinal angiogenesis in the course of the ROP mouse model. Topical application of NGF enhanced while intraocular injections of anti‐NGF neutralizing antibody reduced pathological retinal vascularization in mice subjected to the ROP model. The pro‐angiogenic effect of NGF in the retina was mediated by inhibition of retinal endothelial cell apoptosis. In vitro, NGF decreased the intrinsic (mitochondria‐dependent) apoptosis in hypoxia‐treated human retinal microvascular endothelial cells and preserved the mitochondrial membrane potential. The anti‐apoptotic effect of NGF was associated with increased BCL2 and reduced BAX, as well as with enhanced ERK and AKT phosphorylation, and was abolished by inhibition of the AKT pathway. Our findings reveal an anti‐apoptotic role of NGF in the hypoxic retinal endothelium, which is involved in promoting pathological retinal vascularization, thereby pointing to NGF as a potential target for proliferative retinopathies. 相似文献
33.
Cancer is a worldwide increasing burden and its therapy is often challenging and causes severe side effects in healthy tissue. If drugs are loaded into nanoparticles, side effects can be reduced, and efficiency can be increased via the enhanced permeability and retention effect. This effect is based on the fact that nanoparticles with sizes from 10 to 200 nm can accumulate in tumor tissue due to their leaky vasculature. In this work, we produced polycaprolactone (PCL) in the sizes 1.8, 5.4, and 13.6 kDa and were able to produce spherical shaped nanoparticles with mean diameters of 64 ± 19 nm out of the PCL5.4 and 45 ± 8 nm out of the PCL13.6 reproducibly. By encapsulation of paclitaxel the diameter of that nanoparticles did not increase, and we were able to encapsulate 73 ± 7 fmol paclitaxel per 1000 particles in the PCL5.4‐nanoparticles and 35 ± 8 fmol PTX per 1000 PCL13.6‐nanoparticles. Furthermore, we coupled the aptamer S15 to preformed PCL5.4‐nanoparticles resulting in particles with a hydrodynamic diameter of 153 nm. This offers the opportunity to use these nanoparticles for targeted drug delivery. 相似文献
34.
Lisa N. Barrow Sabrina M. McNew Nora Mitchell Spencer C. Galen Holly L. Lutz Heather Skeen Thomas Valqui Jason D. Weckstein Christopher C. Witt 《Ecology letters》2019,22(6):987-998
Variation in susceptibility is ubiquitous in multi‐host, multi‐parasite assemblages, and can have profound implications for ecology and evolution in these systems. The extent to which susceptibility to parasites is phylogenetically conserved among hosts can be revealed by analysing diverse regional communities. We screened for haemosporidian parasites in 3983 birds representing 40 families and 523 species, spanning ~ 4500 m elevation in the tropical Andes. To quantify the influence of host phylogeny on infection status, we applied Bayesian phylogenetic multilevel models that included a suite of environmental, spatial, temporal, life history and ecological predictors. We found evidence of deeply conserved susceptibility across the avian tree; host phylogeny explained substantial variation in infection status, and results were robust to phylogenetic uncertainty. Our study suggests that susceptibility is governed, in part, by conserved, latent aspects of anti‐parasite defence. This demonstrates the importance of deep phylogeny for understanding present‐day ecological interactions. 相似文献
35.
Paced QRS morphology predicts incident left ventricular systolic dysfunction and atrial fibrillation
Martin van Zyl Chance M. Witt Subir Bhatia Majd Khasawneh Prakriti Gaba Charles J. Lenz Andrew N. Rosenbaum Htin Aung David O. Hodge Christopher J. McLeod Samuel J. Asirvatham 《Indian pacing and electrophysiology journal》2019,19(2):40-46
Background
The prognostic significance of paced QRS complex morphology on surface ECG remains unclear. This study aimed to assess long-term outcomes associated with variations in the paced QRS complex.Methods
Adult patients who underwent dual-chamber pacemaker implantation with 20% or more ventricular pacing and a 12-lead ECG showing a paced complex were included. The paced QRS was analyzed in leads I and aVL. Long-term clinical and echocardiographic outcomes were compared at 5 years.Results
The study included 844 patients (43.1% female; age 75.0?±?12.1). Patients with a longer paced QRS (pQRS) duration in lead I had a lower rate of atrial fibrillation (HR 0.80; p?=?0.03) and higher rate of systolic dysfunction (HR 1.17; p?<?0.001). Total pacing complex (TPC) duration was linked to higher rates of ICD implantation (HR 1.18; p?=?0.04) and systolic dysfunction (HR 1.22, p?<?0.001). Longer paced intrinsicoid deflection (pID) was associated with less atrial fibrillation (HR 0.75; p?=?0.01), more systolic dysfunction (HR 1.17; p?<?0.001), ICD implantation (HR 1.23; p?=?0.04), and CRT upgrade (HR 1.23; p?=?0.03). Exceeding thresholds for TPC, pQRS, and pID of 170, 146, and 112?ms in lead I, respectively, was associated with a substantial increase in systolic dysfunction over 5 years (p?<?0.001).Conclusions
Longer durations of all tested parameters in lead I were associated with increased rates of left ventricular systolic dysfunction. ICD implantation and CRT upgrade were also linked to increased TPC and pID durations. Paradoxically, patients with longer pID and pQRS had less incident atrial fibrillation. 相似文献36.
Witt CC Gerull B Davies MJ Centner T Linke WA Thierfelder L 《The Journal of biological chemistry》2001,276(7):5353-5359
Myosin-binding protein-C (MyBP-C) is a component of all striated-muscle sarcomeres, with a well established structural role and a possible function for force regulation. Multiple mutations within the gene for cardiac MyBP-C, one of three known isoforms, have been linked to familial hypertrophic cardiomyopathy. Here we generated a knock-in mouse model that carries N-terminal-shortened cardiac MyBP-C. The mutant protein was designed to have a similar size as the skeletal MyBP-C isoforms, whereas known myosin and titin binding sites as well as the phosphorylatable MyBP-C motif were not altered. We have shown that mutant cardiac MyBP-C is readily incorporated into the sarcomeres of both heterozygous and homozygous animals and can still be phosphorylated by cAMP-dependent protein kinase. Although histological characterization of wild-type and mutant hearts did not reveal obvious differences in phenotype, left ventricular fibers from homozygous mutant mice exhibited an increased Ca(2+) sensitivity of force development, particularly at lower Ca(2+) concentrations, whereas maximal active force levels remained unchanged. The results allow us to propose a model of how cMyBP-C may affect myosin-head mobility and to rationalize why N-terminal mutations of the protein in some cases of familial hypertrophic cardiomyopathy could lead to a hypercontractile state. 相似文献
37.
Schultz Jel J Glascock BJ Witt SA Nieman ML Nattamai KJ Liu LH Lorenz JN Shull GE Kimball TR Periasamy M 《American journal of physiology. Heart and circulatory physiology》2004,286(3):H1146-H1153
We recently developed a mouse model with a single functional allele of Serca2 (Serca2+/-) that shows impaired cardiac contractility and relaxation without overt heart disease. The goal of this study was to test the hypothesis that chronic reduction in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2 levels in combination with an increased hemodynamic load will result in an accelerated pathway to heart failure. Age-matched wild-type and Serca2+/- mice were subjected to 10 wk of pressure overload via transverse aortic coarctation surgery. Cardiac hypertrophy and heart failure were assessed by echocardiography, gravimetry/histology, hemodynamics, and Western blotting analyses. Our results showed that approximately 64% of coarcted Serca2+/- mice were in heart failure compared with 0% of coarcted wild-type mice (P < 0.05). Overall, morbidity and mortality were greatly increased in Serca2+/- mice under pressure overload. Echocardiography assessment revealed a significant increase in left ventricular (LV) mass, and LV hypertrophy in coarcted Serca2+/- mice converted from a concentric to an eccentric pattern, similar to that seen in human heart failure. Coarcted Serca2+/- mice had decreased contractile/systolic and relaxation/diastolic performance and/or function compared with coarcted wild-type mice (P < 0.05), despite a similar duration and degree of pressure overload. SERCA2a protein levels were significantly reduced (>50%) in coarcted Serca2+/- mice compared with noncoarcted and coarcted wild-type mice. Our findings suggest that reduction in SERCA2 levels in combination with an increased hemodynamic load results in an accelerated pathway to heart failure. 相似文献
38.
Peroxisomal localization of sulfite oxidase separates it from chloroplast-based sulfur assimilation 总被引:6,自引:0,他引:6
Nowak K Luniak N Witt C Wüstefeld Y Wachter A Mendel RR Hänsch R 《Plant & cell physiology》2004,45(12):1889-1894
Recently, we isolated the sulfite oxidase (SO) gene from Arabidopsis thaliana and characterized the purified SO protein. The purpose of the present study was to determine the subcellular localization of this novel plant enzyme. Immunogold electron-microscopic analysis showed the gold labels nearly exclusively in the peroxisomes. To verify this finding, green fluorescent protein was fused to full-length plant SO including the putative peroxisomal targeting signal 1 (PTS1) 'SNL' and expressed in tobacco leaves. Our results showed a punctate fluorescence pattern resembling that of peroxisomes. Co-labelling with MitoTracker-Red excluded that the observed fluorescence was due to mitochondrial sorting. By investigation of deleted or mutated PTS1, no functional peroxisomal targeting signal 2 (PTS2) could be detected in plant SO. This conclusion is supported by expression studies in Pichia pastoris mutants with defined defects either in PTS1- or PTS2-mediated peroxisomal import. 相似文献
39.
Primary ciliary dyskinesia (PCD) is a multisystem disease characterized by recurrent respiratory tract infections, sinusitis, bronchiectasis and male subfertility, associated in about 50% patients with situs inversus totalis (the Kartagener syndrome). The disease phenotype is caused by ultrastructural defects of respiratory cilia and sperm tails. PCD is a heterogenetic disorder, usually inherited as an autosomal recessive trait. So far, mutations in two human genes have been proved to cause the disease. However, the pathogenetics of most PCD cases remains unsolved. In this review, the disease pathomechanism is discussed along with the genes that are or may be involved in the pathogenesis of primary ciliary dyskinesia and the Kartagener syndrome. 相似文献
40.
Apparent X-linked primary ciliary dyskinesia associated with retinitis pigmentosa and a hearing loss
Three brothers, one 10-year-old and a pair of 14-year-old dizygotic twins--expressed the classical, early-onset retinitis pigmentosa (RP) with typical ophthalmoscopic findings, night blindness, visual field constricted to 10 degrees and flat ERG response. All three brothers were also diagnosed with primary ciliary dyskinesia (PCD) and had recurrent respiratory infections, chronic sinusitis and bronchiectasis. In all of them, resection of the middle lobe of the right lung was performed. A similar clinical picture of coexisting RP and PCD was noted in the brother of the probands' mother. All probands displayed situs solitus. Consistent with the X-linked mode of RP inheritance, there were also three obligatory female carriers of the disorder in this family: the mother of the affected boys, her mother and a daughter of her brother. In all of them, retinitis pigmentosa "sine pigmento" was found with milder but clinically significant symptoms (mild night blindness, visual field constricted to 30 degrees, and scotopic and photopic ERG responses reduced to 30-60%). No extraocular symptoms were detected in any of the heterozygous female carriers. This family presents an example of two rare phenomena: X-linked dominant retinitis pigmentosa (with milder expression in females) and a rare combination of RP with recurrent respiratory infections due to PCD. 相似文献