University of Basel

About: University of Basel is a education organization based out in Basel, Basel-Stadt, Switzerland. It is known for research contribution in the topics: Population & Gene. The organization has 25084 authors who have published 52975 publications receiving 2388002 citations. The organization is also known as: Universität Basel & Basel University.

Experimental evidence for the functional relevance of anion– π interactions

Abstract: Attractive in theory and confirmed to exist, anion–π interactions have never really been seen at work. To catch them in action, we prepared a collection of monomeric, cyclic and rod-shaped naphthalenediimide transporters. Their ability to exert anion–π interactions was demonstrated by electrospray tandem mass spectrometry in combination with theoretical calculations. To relate this structural evidence to transport activity in bilayer membranes, affinity and selectivity sequences were recorded. π-acidification and active-site decrowding increased binding, transport and chloride > bromide > iodide selectivity, and supramolecular organization inverted acetate > nitrate to nitrate > acetate selectivity. We conclude that anion–π interactions on monomeric surfaces are ideal for chloride recognition, whereas their supramolecular enhancement by π,π-interactions appears perfect to target nitrate. Chloride transporters are relevant to treat channelopathies, and nitrate sensors to monitor cellular signaling and cardiovascular diseases. A big impact on organocatalysis can be expected from the stabilization of anionic transition states on chiral π-acidic surfaces.

Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch

Abstract: Antigen-experienced memory T cells acquire effector function with innate-like kinetics; however, the metabolic requirements of these cells are unknown. Here we show that rapid interferon-γ (IFN-γ) production of effector memory (EM) CD8(+) T cells, activated through stimulation mediated by the T cell antigen receptor (TCR) and the costimulatory receptor CD28 or through cognate interactions, was linked to increased glycolytic flux. EM CD8(+) T cells exhibited more glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity at early time points, before proliferation commenced, than did naive cells activated under similar conditions. CD28 signaling via the serine-threonine kinase Akt and the metabolic-checkpoint kinase mTORC2 was needed to sustain TCR-mediated immediate-early glycolysis. Unlike glycolysis in proliferating cells, immediate-early glycolysis in memory CD8(+) T cells was rapamycin insensitive. Thus, CD8(+) memory T cells have an Akt-dependent 'imprinted' glycolytic potential that is required for efficient immediate-early IFN-γ recall responses.

Cryo-EM structure of alpha-synuclein fibrils.

Abstract: People with Parkinson’s disease have damaged cells in a part of the brain involved in movement, learning and reward-seeking behaviors. These cells contain blob-like aggregates that contain abnormally high amounts of a protein called alpha-synuclein. It is generally believed that, within these blobs, this protein clusters together into small needles called fibrils. Discerning the structure of a fibril could help researchers to understand both how alpha-synuclein damages brain cells and how diseases like Parkinson’s spread. Biophysicists have attempted to reveal the fibril structure previously. But many of these efforts only looked at short segments of the alpha-synuclein protein. Researchers still need more detailed imagery of the fibrils to confirm previous findings regarding their architecture and ultimately to identify ways to counteract the damage they cause. Guerrero-Ferreira et al. used a technique called cryo-electron microscopy to capture images of frozen fibrils made from a version of human alpha-synuclein that readily aggregates and that is only slightly shorter than the full-length protein. Processing these high-resolution images with computer software then revealed a three-dimensional model of the fibril structure, in which fine details are clearly visible. In the fibril, the proteins cluster to form a helix, similar to a flight of stairs. Each turn of the helix is formed by two alpha-synuclein molecules, facing each other but rotated by almost 180 degrees from one another. The three-dimensional model displays which parts of the protein lie at the core of the helix and thereby stabilize the fibril structure. Guerrero-Ferreira et al. speculate that fibrils may also take alternative forms because common alpha-synuclein mutations, which correlate with disease, would destabilize the observed helical structure. In the future, researchers may be able to use the features of this three-dimensional model to help design molecules that would make the fibrils detectable via medical imaging. This could help doctors to diagnose people with Parkinson’s disease at an earlier stage. Further research is also needed to understand where and how fibrils form, if differences in fibril structures exist within or between patients, possibly leading to different sub-classes of the disease, and how such fibrils interact with and possibly damage human brain cells.

Non-visual effects of light on melatonin, alertness and cognitive performance: can blue-enriched light keep us alert?

Abstract: Light exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance