Role of tyrosine 238 in the active site of Rhodotorula gracilis D-amino acid oxidase - A site-directed mutagenesis study

Y238, one of the very few conserved residues in the active site of d-amino acid oxidases (DAAO), was mutated to phenylalanine and serine in the enzyme from the yeast Rhodotorula gracilis. The mutated proteins are catalytically competent thus eliminating Tyr238 as an active-site acid/base catalyst. Y238F and Y238S mutants exhibit a threefold slower turnover on d-alanine as substrate, which can be attributed to a slower rate of product release relative to the wild-type enzyme (a change of the rate constants for substrate binding was also evident). The Y238 DAAO mutants have spectral properties similar to those of the wild-type enzyme but the degree of stabilization of the flavin semiquinone and the redox properties in the free form of Y238S are different. The binding of the carboxylic acid competitive inhibitors and the substrate d-alanine are changed only slightly, suggesting that the overall substrate binding pocket remains intact. In agreement with data from the pH dependence of ligand binding and with the protein crystal structure, site-directed mutagenesis results emphasize the importance of residue Y238 in controlling access to the active site instead of a role in the substrate/ligand interaction

How Hertzian solitary waves interact with boundaries in a 1-D granular medium

We perform measurements, numerical simulations, and quantitative comparisons with available theory on solitary wave propagation in a linear chain of beads without static preconstrain. By designing a nonintrusive force sensor to measure the impulse as it propagates along the chain, we study the solitary wave reflection at a wall. We show that the main features of solitary wave reflection depend on wall mechanical properties. Since previous studies on solitary waves have been performed at walls without these considerations, our experiment provides a more reliable tool to characterize solitary wave propagation. We find, for the first time, precise quantitative agreements.Comment: Proof corrections, ReVTeX, 11 pages, 3 eps (Focus and related papers on http://www.supmeca.fr/perso/jobs/

Wave localization in strongly nonlinear Hertzian chains with mass defect

We investigate the dynamical response of a mass defect in a one-dimensional non-loaded horizontal chain of identical spheres which interact via the nonlinear Hertz potential. Our experiments show that the interaction of a solitary wave with a light intruder excites localized mode. In agreement with dimensional analysis, we find that the frequency of localized oscillations exceeds the incident wave frequency spectrum and nonlinearly depends on the size of the intruder and on the incident wave strength. The absence of tensile stress between grains allows some gaps to open, which in turn induce a significant enhancement of the oscillations amplitude. We performed numerical simulations that precisely describe our observations without any adjusting parameters.Comment: 4 pages, 5 figures, submitted for publicatio

Intrinsic Energy Localization through Discrete Gap Breathers in One-Dimensional Diatomic Granular Crystals

We present a systematic study of the existence and stability of discrete breathers that are spatially localized in the bulk of a one-dimensional chain of compressed elastic beads that interact via Hertzian contact. The chain is diatomic, consisting of a periodic arrangement of heavy and light spherical particles. We examine two families of discrete gap breathers: (1) an unstable discrete gap breather that is centered on a heavy particle and characterized by a symmetric spatial energy profile and (2) a potentially stable discrete gap breather that is centered on a light particle and is characterized by an asymmetric spatial energy profile. We investigate their existence, structure, and stability throughout the band gap of the linear spectrum and classify them into four regimes: a regime near the lower optical band edge of the linear spectrum, a moderately discrete regime, a strongly discrete regime that lies deep within the band gap of the linearized version of the system, and a regime near the upper acoustic band edge. We contrast discrete breathers in anharmonic FPU-type diatomic chains with those in diatomic granular crystals, which have a tensionless interaction potential between adjacent particles, and highlight in that the asymmetric nature of the latter interaction potential may lead to a form of hybrid bulk-surface localized solutions

Efeito do extrato alcoólico da folha de erva de bugre no desempenho de sementes de feijão.

O trabalho objetivou avaliar o efeito do extrato alcoólico de folha de Erva de Bugre (Casearia sylvestris) na germinação de sementes de feijão (Phaseolus vulgaris)

The Role of Amygdala in Self-Conscious Emotions in a Patient With Acquired Bilateral Damage

Shame plays a fundamental role in the regulation of our social behavior. One intriguing question is whether amygdala might play a role in processing this emotion. In the present single-case study, we tested a patient with acquired damage of bilateral amygdalae and surrounding areas as well as healthy controls on shame processing and other social cognitive tasks. Results revealed that the patient\u2019s subjective experience of shame, but not of guilt, was more reduced than in controls, only when social standards were violated, while it was not different than controls in case of moral violations. The impairment in discriminating between normal social situations and violations also emerged. Taken together, these findings suggest that the role of the amygdala in processing shame might reflect its relevance in resolving ambiguity and uncertainty, in order to correctly detect social violations and to generate shame feelings

Structure of a widely conserved type IV pilus biogenesis factor that affects the stability of secretin multimers

International audienc

Immunomodulation of Myocardial Fibrosis

Immunotherapy is a potential cornerstone in the treatment of myocardial fibrosis. During a myocardial insult or heart failure, danger signals stimulate innate immune cells to produce chemokines and profibrotic cytokines, which initiate self-escalating inflammatory processes by attracting and stimulating adaptive immune cells. Stimulation of fibroblasts by inflammatory processes and the need to replace damaged cardiomyocytes fosters reshaping of the cardiac fibroblast landscape. In this review, we discuss new immunomodulatory strategies that manipulate and direct cardiac fibroblast activation and differentiation. In particular, we highlight immunomodulatory strategies that target fibroblasts such as chimeric antigen receptor T cells, interleukin-11, and invariant natural killer T-cells. Moreover, we discuss the potential of manipulating both innate and adaptive immune system components for the translation into clinical validation. Clearly, multiple pathways should be considered to develop innovative approaches to ameliorate myocardial fibrosis and hence to reduce the risk of heart failure

Maize response to macronutrients and potential for profitability in sub-Saharan Africa

The final publication is available at Springer via http://dx.doi.org/10.1007/s10705-015-9717-2Sub-Saharan Africa (SSA) is plagued by low productivity and little research is available on the attainable responses and profitability to applied nutrients under variable environments. The objective of this study was to determine the attainable maize grain response to and potential of profitability of N, P and K application in SSA using boundary line approaches. Data from experiments conducted in SSA under AfSIS project (2009–2012) and from FAO trials database (1969–1996) in 15 countries and constituting over 375 different experimental locations and 6600 data points are used. Both response to fertilizer and value cost ratio (VCR) are highly variable and no more than 61 % cases for N, 43 % for P and 25 % for K attain VCR of 2 or more. Also, based on the recent AfSIS data, VCR exceeds 1 in just 67 % (N), 57 % (P) and 40 % (K) of the cases, even when best management practices are applied on a research farm, and interest rates are zero. Chances for profitability are highest when soil organic carbon is 1–2 % and control maize grain yield is 1–3 t ha−1 but also depends on relatively static soil properties (primarily texture and mineralogy) that are not under farmer control. We conclude that return on investment of macronutrient fertilizer is highly variable and can be substantially increased by helping farmers decide where to apply the fertilizers. Consequently, farmers need access to information on factors influencing economic returns of fertilizer use in order to make the right decisions