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131.
Dobránszki Judit Hidvégi Norbert Gulyás Andrea Teixeira da Silva Jaime A. 《Plant molecular biology》2019,100(4-5):511-525
Plant Molecular Biology - In response to an ultrasound pulse, several hundred DEGs, including in response to stress, were up- or down-regulated in in vitro potato plantlets. Despite this abiotic... 相似文献
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Chen Cai Timo Itzel Haristi Gaitantzi Carolina de la Torre Emrullah Birgin Johannes Betge Norbert Gretz Andreas Teufel Nuh N. Rahbari Matthias P. Ebert Katja BreitkopfHeinlein 《Journal of cellular and molecular medicine》2022,26(2):343
Colorectal cancer (CRC) is a high‐incidence malignancy worldwide which still needs better therapy options. Therefore, the aim of the present study was to investigate the responses of normal or malignant human intestinal epithelium to bone morphogenetic protein (BMP)‐9 and to find out whether the application of BMP‐9 to patients with CRC or the enhancement of its synthesis in the liver could be useful strategies for new therapy approaches. In silico analyses of CRC patient cohorts (TCGA database) revealed that high expression of the BMP‐target gene ID1, especially in combination with low expression of the BMP‐inhibitor noggin, is significantly associated with better patient survival. Organoid lines were generated from human biopsies of colon cancer (T‐Orgs) and corresponding non‐malignant areas (N‐Orgs) of three patients. The N‐Orgs represented tumours belonging to three different consensus molecular subtypes (CMS) of CRC. Overall, BMP‐9 stimulation of organoids promoted an enrichment of tumour‐suppressive gene expression signatures, whereas the stimulation with noggin had the opposite effects. Furthermore, treatment of organoids with BMP‐9 induced ID1 expression (independently of high noggin levels), while treatment with noggin reduced ID1.In summary, our data identify the ratio between ID1 and noggin as a new prognostic value for CRC patient outcome. We further show that by inducing ID1, BMP‐9 enhances this ratio, even in the presence of noggin. Thus, BMP‐9 is identified as a novel target for the development of improved anti‐cancer therapies of patients with CRC. 相似文献
135.
1. Ionophore-induced osmotic swelling was used to study Cl- transport in isolated rat liver mitochondria. 2. Energy-dependent, neutral ionophore-induced swelling in Cl- salts at pH 7.2 required K+ and was preceded by a brief lag phase that was absent in chlorotributyltin-induced swelling. 3. Treatments that stimulated or inhibited mitochondrial K+/H+ exchange had qualitatively similar effects on both valinomycin-induced swelling and the associated lag phase. 4. The results suggest that valinomycin-induced Cl- permeability results from an interaction between the K+/H+ antiporter and neutral ionophore K+ complexes. 相似文献
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Michelle P. Clark Thao Huynh Shringar Rao Liana Mackiewicz Hugh Mason Shahla Romal Michael D. Stutz Sang H. Ahn Linda Earnest Vitina Sozzi Margaret Littlejohn Bang M. Tran Norbert Wiedemann Elizabeth Vincan Joseph Torresi Hans J. Netter Tokameh Mahmoudi Peter Revill Marc Pellegrini Gregor Ebert 《Cell death & disease》2021,12(7)
A major unmet clinical need is a therapeutic capable of removing hepatitis B virus (HBV) genome from the liver of infected individuals to reduce their risk of developing liver cancer. A strategy to deliver such a therapy could utilize the ability to target and promote apoptosis of infected hepatocytes. Presently there is no clinically relevant strategy that has been shown to effectively remove persistent episomal covalently closed circular HBV DNA (cccDNA) from the nucleus of hepatocytes. We used linearized single genome length HBV DNA of various genotypes to establish a cccDNA-like reservoir in immunocompetent mice and showed that clinical-stage orally administered drugs that antagonize the function of cellular inhibitor of apoptosis proteins can eliminate HBV replication and episomal HBV genome in the liver. Primary human liver organoid models were used to confirm the clinical relevance of these results. This study underscores a clinically tenable strategy for the potential elimination of chronic HBV reservoirs in patients.Subject terms: Target validation, Hepatitis B, Preclinical research, Translational research 相似文献
138.
Plasmonics - We present a plasmonic bandpass filter and refractive index sensor based on perturbed square cavity resonator with slits, which is fed by orthogonally oriented feeding waveguides. The... 相似文献
139.
Ilkovski B Cooper ST Nowak K Ryan MM Yang N Schnell C Durling HJ Roddick LG Wilkinson I Kornberg AJ Collins KJ Wallace G Gunning P Hardeman EC Laing NG North KN 《American journal of human genetics》2001,68(6):1333-1343
Nemaline myopathy (NM) is a clinically and genetically heterogeneous disorder characterized by muscle weakness and the presence of nemaline bodies (rods) in skeletal muscle. Disease-causing mutations have been reported in five genes, each encoding a protein component of the sarcomeric thin filament. Recently, we identified mutations in the muscle alpha-skeletal-actin gene (ACTA1) in a subset of patients with NM. In the present study, we evaluated a new series of 35 patients with NM. We identified five novel missense mutations in ACTA1, which suggested that mutations in muscle alpha-skeletal actin account for the disease in approximately 15% of patients with NM. The mutations appeared de novo and represent new dominant mutations. One proband subsequently had two affected children, a result consistent with autosomal dominant transmission. The seven patients exhibited marked clinical variability, ranging from severe congenital-onset weakness, with death from respiratory failure during the 1st year of life, to a mild childhood-onset myopathy, with survival into adulthood. There was marked variation in both age at onset and clinical severity in the three affected members of one family. Common pathological features included abnormal fiber type differentiation, glycogen accumulation, myofibrillar disruption, and "whorling" of actin thin filaments. The percentage of fibers with rods did not correlate with clinical severity; however, the severe, lethal phenotype was associated with both severe, generalized disorganization of sarcomeric structure and abnormal localization of sarcomeric actin. The marked variability, in clinical phenotype, among patients with different mutations in ACTA1 suggests that both the site of the mutation and the nature of the amino acid change have differential effects on thin-filament formation and protein-protein interactions. The intrafamilial variability suggests that alpha-actin genotype is not the sole determinant of phenotype. 相似文献
140.
Pey R Bach J Schieren G Gretz N Hafner M 《In vitro cellular & developmental biology. Animal》1999,35(10):571-579
Summary Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent human inherited diseases. The main feature
of the disease is the development of renal cysts, first occurring in the proximal tubules, and with time, dominating all segments
of the nephron, leading to end-stage renal disease in 50% of the patients in their fifth decade of life. A therapy for polycystic
kidney disease (PKD) has not yet been developed. Patients coming to end-stage ADPKD require long-term dialysis and/or transplantation.
A suitable animal model to study ADPKD is the spontaneously mutated Han:SPRD (cy/ +) rat, but a method to cultivate Han:SPRD (cy/ +) derived renal cells which preserves their ability to form cyst-like structures in vitro has previously not been reported.
Based on this well-characterized animal model, we developed a cell culture model of renal cyst formation in vitro. When renal
cells of the Han:SPRD (cy/ +) rat were isolated and cultured under conditions that prevent cell-substratum adhesion, large amounts of cyst-like structures
were formed de novo from Han:SPRD (cy/ +) derived renal cells, but only a few from control rat renal cells. In contrast, when cultivated on plastic as monolayer
cultures, Han:SPRD (cy/ +)-derived and control rat-derived renal cells were indistinguishable and did not form cyst-like structures. Immunohistochemical
characterization of the cyst-like structures suggests tubular epithelial origin of the cyst-forming cells. The amount of cysts
formed from Han:SPRD (cy/ +)-derived renal cells grown in a stationary suspension culture is susceptible to modulation by different conditions. Human
cyst fluid and epidermal growth factor both stimulated the formation of cysts from Han:SPRD (cy/ +)-derived renal cells whereas taxol inhibited cystogenesis. In contrast, neither human cyst fluid nor epidermal growth
factor affected the amount of cysts formed by control rat renal cells. As the culture model reported here allows not only
the distinction of PKD-derived tubular epithelium from its normal counterpart, but also the modulation of cyst formation especially
by Han:SPRD (cy/ +)-derived renal cells, it might be a useful prescreening protocol for potential treatments for PKD and thus reduce the
need for animal experiments.
Both authors contributed equally to the work. 相似文献