Search results for "substitut"
showing 10 items of 1337 documents
Slow and fast evolving endosymbiont lineages: positive correlation between the rates of synonymous and nonsynonymous substitution
2015
The availability of complete genome sequences of bacterial endosymbionts with strict vertical transmission to the host progeny opens the possibility to estimate molecular evolutionary rates in different lineages and understand the main biological mechanisms influencing these rates. We have compared the rates of evolution for non-synonymous and synonymous substitutions in nine bacterial endosymbiont lineages, belonging to four clades (Baumannia, Blochmannia, Portiera, and Sulcia). The main results are the observation of a positive correlation between both rates with differences among lineages of up to three orders of magnitude and that the substitution rates decrease over long endosymbioses.…
Human toll-like receptor 4 mutations are associated with susceptibility to invasive meningococcal disease in infancy.
2006
Toll-like receptor 4 (TLR4) is required for efficient recognition of bacterial infections. We investigated an association between 2 TLR4 mutations (Asp 299 Gly and Thr 399 Ile) and meningococcal disease in 197 patients and 214 healthy controls by allele-specific real time polymerase chain reaction and direct sequencing. Although the allele frequency was not higher in the overall patient population, a significantly higher frequency in the 40 patients younger than 12 months of age (P = 0.007) was observed. We conclude that TLR4 mutations represent a risk factor for meningococcal disease in this age group.
Time Use and Food Taxation in Spain
2009
We evaluate the welfare impact of changing the VAT on food in a context in which households can produce home meals for own consumption that compete with meals served in restaurants. Home production of meals requires the combination of food and time inputs. The fiscal treatment in home production of both the inputs and the final product differs from market production of meals, generating different channels of inefficiency. We calibrate a simple general-equilibrium model for the Spanish economy that identifies three types of consumers according to their income, and simulate the effects of some experiments related to how food is taxed. The results suggest that if we focus only on aggregate wel…
Substitution of carcinogenic solvent dichloromethane for the extraction of volatile compounds in a fat-free model food system
2016
International audience; Dichloromethane is known as a very efficient solvent, but, as other halogenated solvents, is recognized as a hazardous product (CMR substance). The objective of the present work is to propose substitution solvent for the extraction of volatile compounds. The most important physico-chemical parameters in the choice of an appropriate extraction solvent of volatile compounds are reviewed. Various solvents are selected on this basis and on their hazard characteristics. The selected solvents, safer than dichloromethane, are compared using the extraction efficiency of volatile compounds from a model food product able to interact with volatile compounds. Volatile compounds …
Functional cysteine-less subunits of the transporter associated with antigen processing (TAP1 and TAP2) by de novo gene assembly
2002
AbstractWithin the adaptive immune system the transporter associated with antigen processing (TAP) plays a pivotal role in loading of peptides onto major histocompatibility (MHC) class I molecules. As a central tool to investigate the structure and function of the TAP complex, we created cysteine-less human TAP subunits by de novo gene synthesis, replacing all 19 cysteines in TAP1 and TAP2. After expression in TAP-deficient human fibroblasts, cysteine-less TAP1 and TAP2 are functional with respect to adenosine triphosphate (ATP)-dependent peptide transport and inhibition by ICP47 from herpes simplex virus. Cysteine-less TAP1 and TAP2 restore maturation and intracellular trafficking of MHC c…
Introduction of histidine residues into avidin subunit interfaces allows pH-dependent regulation of quaternary structure and biotin binding
2003
AbstractIn order to turn the subunit association and biotin binding of avidin into pH-sensitive phenomena, we have replaced individually three amino acid residues in avidin (Met96, Val115 and Ile117) with histidines in the 1–3 interface, and in combination with a histidine conversion in the 1–2 interface (Trp110). The single replacements Met96His and Val115His in the 1–3 interface were found to have a clear effect on the quaternary structure of avidin, since subunit associations of these mutants became pH-dependent. The histidine replacement in the 1–2 interface affected the biotin-binding properties of the mutants, in particular reversibility of binding and protein–ligand complex formation…
Role of HLA-B α-3 domain amino acid position 194 in HIV disease progression
2013
HLA class I molecules play a role in the regulation of innate immune response. Therefore, the interaction of HLA class I molecules with different activating and inhibitory receptors leads to balancing the immune response. Among the different family of receptors, NK receptors KIR3DL1/S1 and LIR1, play a major role. Aim of this study was to evaluate the role of amino acid polymorphic positions of HLA class I molecules interacting with NK receptors in HIV progression. In order to minimize the influence of viral variability, a cohort of children with a nosocomial monophyletic HIV-1 infection from the Benghazi Children Hospital has been evaluated. To assess the role of single amino acid position…
Molecular dynamics studies on HIV-1 protease: a comparison of the flap motions between wild type protease and the M46I/G51D double mutant
2007
The emergence of drug-resistant mutants of HIV-1 is a tragic effect associated with conventional long-treatment therapies against acquired immunodeficiency syndrome. These mutations frequently involve the aspartic protease encoded by the virus; knowledge of the molecular mechanisms underlying the conformational changes of HIV-1 protease mutants may be useful in developing more effective and longer lasting treatment regimes. The flap regions of the protease are the target of a particular type of mutations occurring far from the active site. These mutations modify the affinity for both substrate and ligands, thus conferring resistance. In this work, molecular dynamics simulations were perform…
Oxytocin receptors and cholesterol: interaction and regulation.
2000
Cholesterol affects the ligand binding function of the oxytocin receptor in a highly specific manner. While the structurally-related cholecystokinin receptor shows a strong correlation between the membrane fluidity and its binding function, the oxytocin receptor behaves differently. A stringent and unique requirement of the affinity state of the oxytocin receptor for structural features of the sterol molecule has been found. The molecular requirements differ both from those postulated for sterol-phospholipid interactions and from those known to be necessary for the activity of other proteins. Employing a new detergent-free subcellular fractionation protocol, a two-fold enrichment of the oxy…
Mapping the tRNA binding site on the surface of human DNMT2 methyltransferase.
2012
The DNMT2 enzyme methylates tRNA-Asp at position C38. Because there is no tRNA–Dnmt2 cocrystal structure available, we have mapped the tRNA binding site of DNMT2 by systematically mutating surface-exposed lysine and arginine residues to alanine and studying the tRNA methylation activity and binding of the corresponding variants. After mutating 20 lysine and arginine residues, we identified eight of them that caused large (>4-fold) decreases in catalytic activity. These residues cluster within and next to a surface cleft in the protein, which is large enough to accommodate the tRNA anticodon loop and stem. This cleft is located next to the binding pocket for the cofactor S-adenosyl-l-methion…