Search results for "conte"

Targeting Nonsense: Optimization of 1,2,4-Oxadiazole TRIDs to Rescue CFTR Expression and Functionality in Cystic Fibrosis Cell Model Systems

2020

Cystic fibrosis (CF) patients develop a severe form of the disease when the cystic fibrosis transmembrane conductance regulator (CFTR) gene is affected by nonsense mutations. Nonsense mutations are responsible for the presence of a premature termination codon (PTC) in the mRNA, creating a lack of functional protein. In this context, translational readthrough-inducing drugs (TRIDs) represent a promising approach to correct the basic defect caused by PTCs. By using computational optimization and biological screening, we identified three new small molecules showing high readthrough activity. The activity of these compounds has been verified by evaluating CFTR expression and functionality after…

A systems-wide understanding of photosynthetic acclimation in algae and higher plants

2017

The ability of phototrophs to colonise different environments relies on robust protection against oxidative stress, a critical requirement for the successful evolutionary transition from water to land. Photosynthetic organisms have developed numerous strategies to adapt their photosynthetic apparatus to changing light conditions in order to optimise their photosynthetic yield, which is crucial for life on Earth to exist. Photosynthetic acclimation is an excellent example of the complexity of biological systems, where highly diverse processes, ranging from electron excitation over protein protonation to enzymatic processes coupling ion gradients with biosynthetic activity, interact on drasti…

Quadruplex detection in human cells

2020

Abstract The precise detection of both DNA and RNA quadruplexes in human cells remains challenging. Efforts are being invested to design, synthesize and operate molecular tools to track and detect quadruplexes in cells. Such probes now have sufficient molecular specificity and suitable spectroscopic properties to shed light on quadruplexes in their cellular context, thus providing reliable details about their existence in cells. Herein, the most important steps in this line of development are summarized, from the very first attempts with organometallic complexes to the development of immunodetection technologies; and from in vitro to live-cell investigations performed with cell-permeable qu…

Deciphering human γδ T cell response in cancer: Lessons from tumor‐infiltrating γδ T cells

2020

The finding that γδ T cells are present among tumor-infiltrating lymphocytes in humans suggests they participate in tumor immune surveillance, but their relevance is unclear because the relative abundance of tumor-infiltrating γδ T cells correlates with positive or negative, or even do not correlate with prognosis. This likely depends on the fact that tumor-infiltrating γδ T cells may play substantially different effector or regulatory functions, and correlation with patient's prognosis relies on distinct γδ T cell subsets in the context of the tumor. There is interest to exploit γδ T cells in tumor immunotherapy, but to make this approach successful there is urgent need to fully understand…

2016

In the perinatal as well as the adult CNS, the subventricular zone (SVZ) of the forebrain is the largest and most active source of neural stem cells (NSCs) that generates neurons and oligodendrocytes (OLs), the myelin forming cells of the CNS. Recent advances in the field are beginning to shed light regarding SVZ heterogeneity, with the existence of spatially segregated microdomains that are intrinsically biased to generate phenotypically distinct neuronal populations. Although most research has focused on this regionalization in the context of neurogenesis, newer findings underline that this also applies for the genesis of OLs under the control of specific patterning molecules. In this min…

Cbt modulates Foxo activation by positively regulating insulin signaling in Drosophila embryos.

2018

In late Drosophila embryos, the epidermis exhibits a dorsal hole as a consequence of germ band retraction. It is sealed during dorsal closure (DC), a morphogenetic process in which the two lateral epidermal layers converge towards the dorsal midline and fuse. We previously demonstrated the involvement of the Cbt transcription factor in Drosophila DC. However its molecular role in the process remained obscure. In this study, we used genomic approaches to identify genes regulated by Cbt as well as its direct targets during late embryogenesis. Our results reveal a complex transcriptional circuit downstream of Cbt and evidence that it is functionally related with the Insulin/insulin-like growth…

Perspectives of Pharmacology over the Past 100 Years

2019

It is fitting that the 100th anniversary of the Handbook of Experimental Pharmacology celebrates not only its founding but also the founding of experimental pharmacology as both had their beginnings in Germany. Founded in 1919 by Arthur Heffter (1859–1925) as the “Handbuch der Experimentellen Pharmakologie” and renamed to its current title in 1937, the Handbook has continued to capture the emergence and developments of experimental pharmacology since the initial systematic work of Rudolf Buchheim and his student Oswald Schmiedeberg. Heffter, the first Chairman of the German Society of Pharmacology, was also responsible for isolating mescaline as the active psychedelic component from the pey…

Lycopene and Vascular Health

2018

Lycopene is a lipophilic, unsaturated carotenoid, found in red-colored fruits and vegetables, including tomatoes, watermelon, papaya, red grapefruits, and guava. The present work provides an up to date overview of mechanisms linking lycopene in the human diet and vascular changes, considering epidemiological data, clinical studies, and experimental data. Lycopene may improve vascular function and contributes to the primary and secondary prevention of cardiovascular disorders. The main activity profile of lycopene includes antiatherosclerotic, antioxidant, anti-inflammatory, antihypertensive, antiplatelet, anti-apoptotic, and protective endothelial effects, the ability to improve the metabol…

Characteristics of Wild Pear ( Pyrus glabra Boiss) Seed Oil and Its Oil‐in‐Water Emulsions: A Novel Source of Edible Oil

2017

The observed high consumer demand for edible oils with high oxidative stability resulted in notable efforts to investigate wild plants as new sources of oils and fats. In this context, the fatty acid profile, total tocopherols, tocotrienols and phenolic compounds, as well as oxidative stability parameters such as peroxide value (PV), conjugated dienes (CD), conjugated trienes (CT), anisidine value (AnV), and kinetic parameters of wild pear (Pyrus glabra Boiss.) seed oil as a novel source of edible oil were investigated. In addition, the oil-in-water emulsion was prepared from wild pear seed oil. Considering the fatty acid profile, linoleic (56.8±1.4g/100 g oil) and oleic acid (27.4±0.6 g/10…

Avoided motifs: short amino acid strings missing from protein datasets.

2020

Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins…