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 & Transplantation. The organization has 25084 authors who have published 52975 publications receiving 2388002 citations. The organization is also known as: Universität Basel & Basel University.

A Chemical Approach to Protein Design—Template‐Assembled Synthetic Proteins (TASP)

Abstract: Advances in methodology in both chemistry and molecular biology allow us to take a fresh look at protein science. Chemical synthesis of peptides and site-directed mutagenesis are now standard research tools, paving the way for the construction of new proteins with tailor-made structural and functional properties. The decisive hurdle on the way lies not in the synthesis of the molecules proper but rather in a better understanding of the complex folding pathways of polypeptide chains into spatially well-defined structures. Can the chemist use his synthetic tools to bypass the notorious “folding problem?” In this article, we present a new approach developed in our laboratory, which opens a chemical route to artificial proteins with predetermined three-dimensional structures, allowing a first step towards the synthesis of new proteins with functional properties.

Caspase-11 activates a canonical NLRP3 inflammasome by promoting K(+) efflux.

Abstract: Recognition of microbe-associated molecular patterns or endogenous danger signals by a subset of cytosolic PRRs results in the assembly of multiprotein signaling complexes, the so-called inflammasomes. Canonical inflammasomes are assembled by NOD-like receptor (NLR) or PYHIN family members and activate caspase-1, which promotes the induction of pyroptosis and the release of mature interleukin-1β/-18. Recently, a noncanonical inflammasome pathway was discovered that results in caspase-11 activation in response to bacterial lipopolysaccharide (LPS) in the cytosol. Interestingly, caspase-11 induces pyroptosis by itself, but requires NLRP3, the inflammasome adapter ASC, and caspase-1 to promote cytokine secretion. Here, we have studied the mechanism by which caspase-11 controls IL-1β secretion. Investigating NLRP3/ASC complex formation, we find that caspase-11 functions upstream of a canonical NLRP3 inflammasome. The activation of NLRP3 by caspase-11 during LPS transfection is a cell-intrinsic process and is independent of the release of danger signals. Furthermore, we show that active caspase-11 leads to a drop of intracellular potassium levels, which is necessary to activate NLRP3. Our study, therefore, sheds new light on the mechanism of noncanonical inflammasome signaling.

Type Ia Supernovae: Influence of the Initial Composition on the Nucleosynthesis, Light Curves, and Spectra and Consequences for the Determination of ΩM and Λ

Abstract: The influence of the initial composition of the exploding white dwarf on the nucleosynthesis, light curves, and spectra of Type Ia supernovae has been studied in order to evaluate the size of evolutionary effects on cosmological timescales, how the effects can be recognized, and how one may be able to correct for them. The calculations are based on a set of delayed detonation models that give a good account of the optical and infrared light curves and of the spectral evolution. The explosions and light curves are calculated using a one-dimensional Lagrangian radiation-hydro code including a nuclear network. Spectra are computed for various epochs using the structure resulting from the light-curve code. Our non-LTE code solves the relativistic radiation transport equations in the comoving frame consistently with the statistical equations and ionization due to γ-radiation for the most important elements (C, O, Ne, Na, Mg, Si, S, Ca, Fe, Co, Ni). About 106 additional lines are included assuming LTE-level populations and an equivalent-two-level approach for the source functions. Changing the initial metallicity Z from Population I to Population II alters the isotopic composition of the outer layers of the ejecta that have undergone explosive O burning. Especially important is the increase of the 54Fe production with metallicity. The influence on the resulting rest-frame visual and blue light curves is found to be small. Detailed analysis of spectral evolution should permit a determination of the progenitor metallicity. Mixing 56Ni into the outer layers during the explosion can produce effects similar to an increased initial metallicity. Mixing can be distinguished from metallicity effects by means of the strong cobalt and nickel lines, by a change of the calcium lines in the optical and IR spectra and, in principle, by γ-ray observations. As the C/O ratio of the white dwarf is decreased, the explosion energy and the 56Ni production are reduced, and the Si-rich layers are more confined in velocity space. A reduction of the C/O ratio by about 60% gives slower rise times by about three days, an increased luminosity at maximum light, a somewhat faster postmaximum decline, and a larger ratio between maximum light and 56Ni tail. A reduction of the C/O ratio has an effect on the colors, light-curve shapes and element distribution similar to a reduction in the deflagration to detonation transition density. However, for the same light-curve shape, the absolute brightness is larger for smaller C/O ratios. An independent determination of the initial C/O ratio and the transition density is possible for local supernovae if detailed analyses of both the spectra and light curves are performed simultaneously. Because the spectra are shifted into different color bands at different redshifts, the effect of metallicity Z on a given observed color is a strong function of redshift. A change of Z by a factor of 3 or of the C/O ratio by 33% alters the peak magnitudes in the optical wavelength range by up to ≈ 0.3 mag for z ≥ 0.2. These variations are comparable to the effect of changes of ΩM and Λ at redshifts of 0.5-1.0. The systematic effects due to changes in composition are expected to remain small up to about z ≈ 0.5 for R-V and up to z ≈ 0.7 for R-I. We discuss how evolution in the progenitor population can be recognized and taken into account. With proper account of evolutionary corrections, supernovae will provide a valuable tool to determine the cosmological parameters of the universe, and they will provide new insight into its chemical evolution.

Incorporating considerations of resources use into grading recommendations

Abstract: Guideline panellists have differing opinions on whether resource use should influence decisions on individual patients. As medical care costs rise, resource use considerations become more compelling, but panellists may find dealing with such considerations challenging

Mapping and predicting mortality from systemic sclerosis

Abstract: Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.