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91.

Background  

The electroencephalogram (EEG) reflects the electrical activity in the brain on the surface of scalp. A major challenge in this field is the localization of sources in the brain responsible for eliciting the EEG signal measured at the scalp. In order to estimate the location of these sources, one must correctly model the sources, i.e., dipoles, as well as the volume conductor in which the resulting currents flow. In this study, we investigate the effects of dipole depth and orientation on source localization with varying sets of simulated random noise in 4 realistic head models.  相似文献   
92.
The hydantoin transporter Mhp1 is a sodium‐coupled secondary active transport protein of the nucleobase‐cation‐symport family and a member of the widespread 5‐helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site‐directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5‐substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5‐substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5‐(2‐naphthylmethyl)‐L‐hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1.  相似文献   
93.

Background  

The functional and structural characterisation of enzymes that belong to microbial metabolic pathways is very important for structure-based drug design. The main interest in studying shikimate pathway enzymes involves the fact that they are essential for bacteria but do not occur in humans, making them selective targets for design of drugs that do not directly impact humans.  相似文献   
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We address the problem of the possible significance of biological speciation to the magnitude and pattern of divergence of asexually transmitted characters in bisexual species. The empirical data for this report consist of restriction endonuclease site variability in maternally transmitted mitochondrial DNA (mtDNA) isolated from 82 samples of Peromyscus polionotus and P. leucopus collected from major portions of the respective species' ranges. Data are analyzed together with previously published information on P. maniculatus, a sibling species to polionotus. Maps of restriction sites indicate that all of the variation observed can be reasonably attributed to base substitutions leading to loss or gain of particular recognition sites. Magnitude of mtDNA sequence divergence within polionotus (maximum approximately equal to 2%) is roughly comparable to that observed within any of five previously identified mtDNA assemblages in maniculatus. Sequence divergence within leucopus (maximum approximately equal to 4%) is somewhat greater than that within polionotus. Consideration of probable evolutionary links among mtDNA restriction site maps allowed estimation of matriarchal phylogenies within polionotus and leucopus. Clustering algorithms and qualitative Wagner procedures were used to generate phenograms and parsimony networks, respectively, for the between-species comparisons. Three simple graphical models are presented to illustrate some conceivable relationships of mtDNA differentiation to speciation. In theoretical case I, each of two reproductively defined species (A and B) is monophyletic in matriarchal genealogy; the common female ancestor of either species can either predate or postdate the speciation. In case II, neither species is monophyletic in matriarchal genotype. In case III, species B is monophyletic but forms a subclade within A which is thus paraphyletic with respect to B. The empirical results for mtDNA in maniculatus and polionotus appear to conform closely to case III. These theoretical and empirical considerations raise a number of questions about the general relationship of the speciation process to the evolution of uniparentally transmitted traits. Some of these considerations are presented, and it is suggested that the distribution patterns of mtDNA sequence variation within and among extant species should be of considerable relevance to the particular demographies of speciation.   相似文献   
99.
A gently undulating to flat erosion surface with shallow-water borings and burrows is present in the midst of a Sangamonian (Eemian; marine oxygen isotope substage 5e) reefal facies on the islands of San Salvador and Great Inagua, Bahamas. Precise U/Th dating of corals above and below this surface show that it formed around 125-124 ka, and that the sea-level regressive-transgressive cycle which produced it lasted for 1500 years or less. The surface occurs on entirely carbonate rocks and has a low relief punctuated by erosional channels and karstic caves formed during the sea-level lowstand. A terra rossa paleosol, developed during that lowstand, partially fills a set of large lithophagid bivalve borings ( Gastrochaenolites torpedo ), showing that they were excavated during the regression. Rhizomorphs formed by plant roots occur on the erosion surface at Great Inagua. Extensive boring of the upward-facing surfaces occurred during the ensuing transgression, including a smaller G. torpedo and a clionid sponge boring ( Entobia ovula ). The bored surface is encrusted by a variety of shallow-water corals and, eventually, the re-established bank-barrier coral reefs. A sparse assemblage of serpulid worm and vermicularid gastropod tubes encrusted the channel and cave walls. Robust Ophiomorpha burrow systems occur within pockets of sediment in the coral facies both below and above the erosion surface. The channels and caves are filled with transgressive calcarenitic sediments in which occur numerous Ophiomorpha and Skolithos burrows. The ichnofossils on, below, and above this erosion surface are prominent indicators of a short-lived but significant global sea-level event.  相似文献   
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