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1.
Jeff A Johnson Heather RL Lerner Pamela C Rasmussen David P Mindell 《BMC evolutionary biology》2006,6(1):65-12
Background
Populations of the Oriental White-backed Vulture (Gyps bengalensis) have declined by over 95% within the past decade. This decline is largely due to incidental consumption of the non-steroidal anti-inflammatory veterinary pharmaceutical diclofenac, commonly used to treat domestic livestock. The conservation status of other Gyps vultures in southern Asia is also of immediate concern, given the lack of knowledge regarding status of their populations and the continuing existence of taxonomic uncertainties. In this study, we assess phylogenetic relationships for all recognized species and the majority of subspecies within the genus Gyps. The continuing veterinary use of diclofenac is an unknown but potential risk to related species with similar feeding habits to Gyps bengalensis. Therefore, an accurate assessment of the phylogenetic relationships among Gyps vultures should aid in their conservation by clarifying taxonomic uncertainties, and enabling inference of their respective relatedness to susceptible G. bengalensis. 相似文献2.
3.
Summary The transience of caffeine-induced tensions in crayfish muscle fibers indicates a caffeine-insensitive, Ca-transport system in these fibers. Analysis of the changes in relaxation time of caffeine tensions following ionic substitutions in the crayfish saline leads to the conclusions that this Ca-transport system is located in the sarcolemma and that the extrusion process involves binding of external cations, in particular Na. 相似文献
4.
5.
alpha 1-Proteinase inhibitor (alpha 1-PI), a member of the serine
proteinase inhibitor superfamily, has a primary role in controlling
neutrophil elastase activity within the mammalian circulation. Several
studies have indicated that the reactive center region of alpha 1-PI, the
amino acid sequence of which is critical to recognition of and binding to
target proteinases, is highly divergent within and among species. This
appears to be a consequence of accelerated rates of evolution that may have
been driven by positive Darwinian selection. In order to examine this and
other features of alpha 1-PI evolution in more detail, we have isolated and
sequenced cDNAs representing alpha 1- PI mRNAs of the mouse species Mus
saxicola and Mus minutoides and have compared these with a number of other
mammalian alpha 1-PI mRNAs. Relative to other mammalian mRNAs, the extent
of nonsynonymous substitution is generally high throughout the alpha 1-PI
mRNA molecule, indicating greater overall rates of amino acid substitution.
Within and among mouse species, the 5'-half of the mRNA, but not the
3'-half, has been homogenized by concerted evolution. Finally, the reactive
center is under diversifying or positive Darwinian selection in murid
rodents (rats, mice) and guinea pigs yet is under purifying selection in
primates and artiodactyls. The significance of these findings to alpha 1-PI
function and the possible selective forces driving evolution of serpins in
general are discussed.
相似文献
6.
Abstract Three-dimensional structures of cytochrome P450 2B1 were modeled based on the crystallographic structure of P450(cam). The effect of the alignment, loop choice, and minimization with or without water was assessed. Although final models were similar in overall structure, the identity of active site residues depended upon the alignment. An example is Phe-206, which may or may not form part of the active site. The choice of the loop conformation had a lesser effect, while including water in the final minimization step was essential for preserving the shape and size of the active site. The best model (model 2) was in good agreement with the data from site-directed mutagenesis studies, and correctly predicted the effect of substitutions at 9 out of 10 amino acid positions. Thus, residues important for P450 2B1 activity, such as Ile- 114, Phe-206, Ile-290, Thr-302, Val-363, and Gly-478, constitute part of the active site and are able to interact with the substrate androstenedione through hydrophobic interactions. On the other hand, Ser-303, Ser-360 and Lys-473 are far from the active site and/or cannot interact with the substrate, in agreement with experimental data. The model indicates other residues likely to be important for enzyme function, such as Tyr- 111, Leu-209, Ile-477, and Ile- 480, which can be tested experimentally. The substrate may assume numerous binding orientations consistent with observed patterns of hydroxylation at C(5) and C(6). The replacement in the model of certain amino acid residues to mimic residue substitutions from site-directed mutagenesis studies and docking of the substrate into the modified active site allowed a plausible explanation for alterations in regio- and stereospecificities of some mutants of P450 2B1, such as Gly-478 → Ala or Val-363 Ala. 相似文献
7.
Mitochondrial DNA polymorphisms in subterranean mole-rats of the Spalax ehrenbergi superspecies in Israel, and its peripheral isolates 总被引:1,自引:0,他引:1
Nevo E; Honeycutt RL; Yonekawa H; Nelson K; Hanzawa N 《Molecular biology and evolution》1993,10(3):590-604
Patterns of mitochondrial DNA (mtDNA) variation were examined in 133
mole-rats constituting all four chromosomal species (2n = 52, 2n = 54, 2n =
58, and 2n = 60) of the Spalax ehrenbergi superspecies in Israel, as well
as the peripheral isolates of 2n = 60. In the main range of the complex, a
total of 28 mtDNA haplotypes were found in 64 mole-rats, with most
haplotypes being unique to either a single chromosomal species or
population. mtDNA divergence increased from low to high diploid number in a
north-to-south direction in Israel. Overall levels of mtDNA diversity were
unexpectedly the highest in the 2n = 60, the youngest species of the
complex. The mtDNA haplotypes can be separated into two major groups, 2n =
52-54 and 2n = 58-60, and a phylogenetic analysis for each group revealed
evidence of a few haplotypes not sorted by diploid number. The overall
patterns of mtDNA divergence seen within and among the four chromosomal
species are consistent with the parapatric mode of speciation as suggested
from previous studies of allozyme and DNA hybridization. In a separate data
set the patterns of mtDNA variation were examined across the main
geographic range and across peripheral semi-isolates and isolates of the 2n
= 60 chromosomal species. Fifteen haplotypes were found in 69 mole-rats.
High levels of mtDNA diversity characterized the main range, semi-isolated,
and even some desert isolated populations. The peripheral isolates contain
much mtDNA diversity, including novel haplotypes.
相似文献
8.
9.
Abstract While it is well established that classical hydrogen bonds play an important role in enzyme structure, function and dynamics, the role of weaker, but ‘activated’ C-H donor hydrogen bonds is poorly understood. The most important such case involves histidine which often plays a direct role in enzyme catalysis and possesses the most acidic C-H donor group of the standard amino acids. In the present study, we obtained optimized geometries and hydrogen bond interaction energies for C-H…O hydrogen bonded complexes between methane, ethylene, benzene, acetylene, and imidazole with water at the MP2-FC/6-31++G(2d,2p) and MP2-FC/aug-cc-pVDZ//MP2-FC/6-31++G(2d,2p) levels of theory. A strong linear relationship is obtained between the stability of the various hydrogen bonded complexes and both separation distances for H…0 and C—O. In general, these calculations indicate that C-H…0 interactions can be classified as hydrogen bonding interactions, albeit significantly weaker than the classical hydrogen bonds, but significantly stronger than just van der Waals interactions. For instance, while the electronic energy of stabilization at the MP2-FC/aug-cc-pVDZ//MP2-FC/6-31++G(2d,2p) level of theory of a water C-H…O water hydrogen bond is 4.36 kcal/mol more stable than the methane C-H…O water interaction, the water-water hydrogen bond is only 2.06 kcal/mol more stable than the imidazole Ce?H…O water hydrogen bond. Neglecting this latter hydrogen bonding interaction is obviously unacceptable. We next compare the potential energy surfaces for the imidazole Ce?H…O water and imidazole Nd?H…O hydrogen bonded complexes computed at the MP2/6-31++G(2d,2p) level of theory with the potential energy surface computed using the AMBER molecular mechanics program and forcefields. While the Weiner et al and Cornell et al AMBER forcefields reasonably account for the imidazole N-H…O water interaction, these forcefields do not adequately account for the imidazole Ce?H…O water hydrogen bond. A forcefield modification is offered that results in excellent agreement between the ab initio and molecular mechanics geometry and energy for this C-H…O hydrogen bonded complex. 相似文献
10.
Platon Eliseev Grigory Balantcev Elena Nikishova Anastasia Gaida Elena Bogdanova Donald Enarson Tara Ornstein Anne Detjen Russell Dacombe Elena Gospodarevskaya Patrick P. J. Phillips Gillian Mann Stephen Bertel Squire Andrei Mariandyshev 《PloS one》2016,11(4)
BackgroundIn the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy.MethodsA culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm.ResultsAmong smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes were better in LPA-based algorithm compared to culture-based algorithm (p = 0.003). Treatment success rates at 20 months of treatment were higher in patients diagnosed with the LPA-based algorithm (65.2%) as compared to those diagnosed with the culture-based algorithm (44.8%). Mortality was also lower in the LPA-based algorithm group (7.6%) compared to the culture-based algorithm group (15.9%). There was no statistically significant difference in smear and culture conversion rates between the two algorithms.ConclusionThe results of the study suggest that the introduction of LPA leads to faster time to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics. 相似文献