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Uri Obolski, Eynat Dellus-Gur, Gideon Y Stein, Lilach Hadany
INTRODUCTION: Antibiotic resistance is an important public health issue, and vast resources are invested in researching new ways to fight it. Recent experimental works have shown that resistance to some antibiotics can result in increased susceptibility to others, namely induce cross-sensitivity. This phenomenon could be utilized to increase efficiency of antibiotic treatment strategies that minimize resistance. However, as conditions in experimental settings and in the clinic may differ substantially, the implications of cross-sensitivity for clinical settings are not guaranteed and should be examined...
June 2016: Infection, Genetics and Evolution
Eynat Dellus-Gur, Mikael Elias, Emilia Caselli, Fabio Prati, Merijn L M Salverda, J Arjan G M de Visser, James S Fraser, Dan S Tawfik
Epistasis is a key factor in evolution since it determines which combinations of mutations provide adaptive solutions and which mutational pathways toward these solutions are accessible by natural selection. There is growing evidence for the pervasiveness of sign epistasis--a complete reversion of mutational effects, particularly in protein evolution--yet its molecular basis remains poorly understood. We describe the structural basis of sign epistasis between G238S and R164S, two adaptive mutations in TEM-1 β-lactamase--an enzyme that endows antibiotics resistance...
July 17, 2015: Journal of Molecular Biology
Eynat Dellus-Gur, Agnes Toth-Petroczy, Mikael Elias, Dan S Tawfik
Protein evolvability includes two elements--robustness (or neutrality, mutations having no effect) and innovability (mutations readily inducing new functions). How are these two conflicting demands bridged? Does the ability to bridge them relate to the observation that certain folds, such as TIM barrels, accommodate numerous functions, whereas other folds support only one? Here, we hypothesize that the key to innovability is polarity--an active site composed of flexible, loosely packed loops alongside a well-separated, highly ordered scaffold...
July 24, 2013: Journal of Molecular Biology
Yakov Kipnis, Eynat Dellus-Gur, Dan S Tawfik
In nature, the evolution of new protein functions is driven not only by side-chain substitutions (point mutations), but also by backbone modifications (insertions and deletions). The current laboratory diversification methods, however, are largely limited to point mutations. Of particular interest are short insertions-by-duplication that are frequent in nature but cannot be introduced in vitro in a library format (i.e. in random locations and lengths). Here, we describe a new procedure that allows the generation of tandem repeats of random fragments of the target gene via rolling-circle amplification, and the concurrent incorporation of these repeats into the target gene...
September 2012: Protein Engineering, Design & Selection: PEDS
Nicola Dellus, Tsuyoshi Kato, Nathalie Saffon-Merceron, Vicenç Branchadell, Antoine Baceiredo
The mixed P,S-bisylide 1 reacts with phosphenium salts, affording phosphoniophosphinocarbenes, with elimination of diphenyl sulfide. Using a more compact cyclic phosphenium cation, the reaction leads to the formation of an original three-membered heterocycle featuring a gem-bisylide function. This molecule represents the first isolable analogue of the phosphirenyl anion derivative.
September 5, 2011: Inorganic Chemistry
Merijn L M Salverda, Eynat Dellus, Florien A Gorter, Alfons J M Debets, John van der Oost, Rolf F Hoekstra, Dan S Tawfik, J Arjan G M de Visser
Whether evolution is erratic due to random historical details, or is repeatedly directed along similar paths by certain constraints, remains unclear. Epistasis (i.e. non-additive interaction between mutations that affect fitness) is a mechanism that can contribute to both scenarios. Epistasis can constrain the type and order of selected mutations, but it can also make adaptive trajectories contingent upon the first random substitution. This effect is particularly strong under sign epistasis, when the sign of the fitness effects of a mutation depends on its genetic background...
March 2011: PLoS Genetics
Nicolas Dellus, Tsuyoshi Kato, Xavier Bagán, Nathalie Saffon-Merceron, Vicenç Branchadell, Antoine Baceiredo
No abstract text is available yet for this article.
September 10, 2010: Angewandte Chemie
A F Zoila
Nevroses and dellusions are self-induced language in which the uttered statement is implemented in an immanent and intransive way, through the psycho-pathological language itself. The narrative pattern and the pathological process are closely linked together in the same two-sided utterance, clinical and at the same time narratological; as is demonstrated by the analysis of two cases.
December 1978: Annales Médico-psychologiques
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