Evolutionary aspects in evaluating mutations in the melanocortin 4 receptor

More than 70 missense mutations have been identified in the human melanocortin 4 receptor (MC4R), and many of them have been associated with obesity. In a number of cases, the causal link between mutations in MC4R and obesity is controversially discussed. Here, we mined evolution as an additional source of structural information that may help to evaluate the functional relevance of naturally occurring variations in MC4R. The sequence information of more than 60 MC4R orthologs enabled us to identify residues that are important for maintaining receptor function. More than 90% of all inactivating mutations found in obese patients were located at amino acid positions that are highly conserved during 450 million years of MC4R evolution in vertebrates. However, for a reasonable number of MC4R variants, we found no correlation between structural conservation of the mutated position and the reported functional consequence. By re-evaluating selected mutations in the MC4R, we demonstrate the usefulness of combining functional and evolutionary approaches

Clinical relevance of biomarkers of oxidative stress

SIGNIFICANCE Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 00, 000-000

Space QUEST mission proposal: experimentally testing decoherence due to gravity

Models of quantum systems on curved space-times lack sufficient experimental verification. Some speculative theories suggest that quantum properties, such as entanglement, may exhibit entirely different behavior to purely classical systems. By measuring this effect or lack thereof, we can test the hypotheses behind several such models. For instance, as predicted by Ralph and coworkers [T C Ralph, G J Milburn, and T Downes, Phys. Rev. A, 79(2):22121, 2009, T C Ralph and J Pienaar, New Journal of Physics, 16(8):85008, 2014], a bipartite entangled system could decohere if each particle traversed through a different gravitational field gradient. We propose to study this effect in a ground to space uplink scenario. We extend the above theoretical predictions of Ralph and coworkers and discuss the scientific consequences of detecting/failing to detect the predicted gravitational decoherence. We present a detailed mission design of the European Space Agency's (ESA) Space QUEST (Space - Quantum Entanglement Space Test) mission, and study the feasibility of the mission schema.Comment: 18 pages, 13 figures, included radiation damage to detectors in appendi