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ion in A. niger.Historians and biologists identify the debate between mechanists and vitalists over the nature of life itself with the arguments of Driesch, Loeb, and other prominent voices. But what if the conversation was broader and the consequences deeper for the field? Following Selleck Luminespib of Joseph Needham in the 1930s and Francis Crick in the 1960s, we deployed tools of the digital humanities to an old problem in the history of biology. We analyzed over 31,000 peer-reviewed scientific papers and learned that bioexceptionalism participated in a robust discursive landscape throughout subfields of the life sciences, occupied even by otherwise unknown biologists.Humans and animals live in social relationships shaped by actions of approach and avoidance. Both are crucial for normal physical and mental development, survival, and well-being. Active withdrawal from social interaction is often induced by the perception of threat or unpleasant social experience and relies on adaptive mechanisms within neuronal networks associated with social behavior. In case of confrontation with overly strong or persistent stressors and/or dispositions of the affected individual, maladaptive processes in the neuronal circuitries and its associated transmitters and modulators lead to pathological social avoidance. This review focuses on active, fear-driven social avoidance, affected circuits within the mesocorticolimbic system and associated regions and a selection of molecular modulators that promise translational potential. A comprehensive review of human research in this field is followed by a reflection on animal studies that offer a broader and often more detailed range of analytical methodologies. Finally, we take a critical look at challenges that could be addressed in future translational research on fear-driven social avoidance.Membrane remodeling is a critical process for many membrane trafficking events, including clathrin-mediated endocytosis. Several molecular mechanisms for protein-induced membrane curvature have been described in some detail. Contrary, the effect that the physico-chemical properties of the membrane have on these processes is far less well understood. Here, we show that the membrane binding and curvature-inducing ENTH domain of epsin1 is regulated by phosphatidylserine (PS). ENTH binds to membranes in a PI(4,5)P2-dependent manner but only induces curvature in the presence of PS. On PS-containing membranes, the ENTH domain forms rigid homo-oligomers and assembles into clusters. Membrane binding and membrane remodeling can be separated by structure-to-function mutants. Such oligomerization mutants bind to membranes but do not show membrane remodeling activity. In vivo, they are not able to rescue defects in epidermal growth factor receptor (EGFR) endocytosis in epsin knock-down cells. Together, these data show that the membrane lipid composition is important for the regulation of protein-dependent membrane deformation during clathrin-mediated endocytosis.Intrinsic disorder can be found in all proteomes of all kingdoms of life and in viruses, being particularly prevalent in the eukaryotes. We conduct a comprehensive analysis of the intrinsic disorder in the human proteins while mapping them into 24 compartments of the human cell. In agreement with previous studies, we show that human proteins are significantly enriched in disorder relative to a generic protein set that represents the protein universe. #link# In fact, the fraction of proteins with long disordered regions and the average protein-level disorder content in the human proteome are about 3 times higher than in the protein universe. Furthermore, levels of intrinsic disorder in the majority of human subcellular compartments significantly exceed the average disorder content in the protein universe. Relative to the overall amount of disorder in the human proteome, proteins localized in the nucleus and cytoskeleton have significantly increased amounts of disorder, measured by both high disorder content and presence of multiple long intrinsically disordered regions. We empirically demonstrate that, on average, human proteins are assigned to 2.3 subcellular compartments, with proteins localized to few subcellular compartments being more disordered than the proteins that are localized to many compartments. Functionally, the disordered proteins localized in the most disorder-enriched subcellular compartments are primarily responsible for interactions with nucleic acids and protein partners. This is the first-time disorder is comprehensively mapped into the human cell. Our observations add a missing piece to the puzzle of functional disorder and its organization inside the cell.
The effect of lens decentration and tilt on retinal image quality has been extensively studied in the past in simulations and clinical studies. The purpose of this study was to analyze the effect of combined lens decentration and tilt on the induction of defocus, astigmatism and coma in phakic and pseudophakic eyes.
Simulations were performed with Zemax on the Liou-Brennan schematic model eye. Based on the position of the gradient lens the image plane was determined (best focus). The lens was decentered horizontally from -1.0 mm to 1.0 mm in steps of 0.2 mm and tilted with respect to the vertical axis from -10° to 10° in steps of 2° (in total 121 combinations of decentration and tilt). For each combination of decentration and tilt defocus, astigmatism (in 0/180°) and horizontal coma was extracted from wave front error and recorded for apupil size of 4 mm. After replacement of the gradient lens with an aberration correcting artificial lens implant model with the equatorial plane of the artificial lens aligcentered or tilted artificial lens implant the postoperative refraction does not match the target refraction or the resulting astigmatism after cataract surgery is not fully explained by measurement of corneal astigmatism.
In this simulation study the effect of a combination of lens decentration in horizontal direction and tilt with respect to the vertical axis on defocus, astigmatism and horizontal coma was analyzed. The results may help to describe in clinical routine if with a decentered or tilted artificial lens implant the postoperative refraction does not match the target refraction or the resulting astigmatism after cataract surgery is not fully explained by measurement of corneal astigmatism.
Homepage: https://www.selleckchem.com/products/NVP-AUY922.html
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