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21.
Phylogenetic relationships were determined for 76 partial P-element
sequences from 14 species of the melanogaster species group within the
Drosophila subgenus Sophophora. These results are examined in the context
of the phylogeny of the species from which the sequences were isolated.
Sequences from the P-element family fall into distinct subfamilies, or
clades, which are often characteristic for particular species subgroups.
When examined locally among closely related species, the evolution of P
elements is characterized by vertical transmission, whereby the P-element
phylogeny traces the species phylogeny. On a broader scale, however, the
P-element phylogeny is not congruent with the species phylogeny. One
feature of P-element evolution in the melanogaster group is the presence of
more than one P-element subfamily, differing by as much as 36%, in the
genomes of some species. Thus, P elements from several individual species
are not monophyletic, and a likely explanation for the incongruence between
P-element and species phylogenies is provided by the comparison of
paralogous sequences. In certain instances, horizontal transfer seems to be
a valid alternative explanation for lack of congruence between species and
P-element phylogenies. The canonical P-element subfamily, which represents
the active, autonomous transposable element, is restricted to D.
melanogaster. Thus, its origin clearly lies outside of the melanogaster
species group, consistent with the earlier conclusion of recent horizontal
transfer.
相似文献
22.
Alan Birchall M. Puncher J. Harrison A. Riddell M. R. Bailey V. Khokryakov S. Romanov 《Radiation and environmental biophysics》2010,49(2):203-212
Epidemiological studies of the relationship between risk and internal exposure to plutonium are clearly reliant on the dose
estimates used. The International Commission on Radiological Protection (ICRP) is currently reviewing the latest scientific
information available on biokinetic models and dosimetry, and it is likely that a number of changes to the existing models
will be recommended. The effect of certain changes, particularly to the ICRP model of the respiratory tract, has been investigated
for inhaled forms of 239Pu and uncertainties have also been assessed. Notable effects of possible changes to respiratory tract model assumptions are
(1) a reduction in the absorbed dose to target cells in the airways, if changes under consideration are made to the slow clearing
fraction and (2) a doubling of absorbed dose to the alveolar region for insoluble forms, if evidence of longer retention times
is taken into account. An important factor influencing doses for moderately soluble forms of 239Pu is the extent of binding of dissolved plutonium to lung tissues and assumptions regarding the extent of binding in the
airways. Uncertainty analyses have been performed with prior distributions chosen for application in epidemiological studies.
The resulting distributions for dose per unit intake were lognormal with geometric standard deviations of 2.3 and 2.6 for
nitrates and oxides, respectively. The wide ranges were due largely to consideration of results for a range of experimental
data for the solubility of different forms of nitrate and oxides. The medians of these distributions were a factor of three
times higher than calculated using current default ICRP parameter values. For nitrates, this was due to the assumption of
a bound fraction, and for oxides due mainly to the assumption of slower alveolar clearance. This study highlights areas where
more research is needed to reduce biokinetic uncertainties, including more accurate determination of particle transport rates
and long-term dissolution for plutonium compounds, a re-evaluation of long-term binding of dissolved plutonium, and further
consideration of modeling for plutonium absorbed to blood from the lungs. 相似文献
23.
Malamas MS Robichaud A Erdei J Quagliato D Solvibile W Zhou P Morris K Turner J Wagner E Fan K Olland A Jacobsen S Reinhart P Riddell D Pangalos M 《Bioorganic & medicinal chemistry letters》2010,20(22):6597-6605
The identification of small molecule aminohydantoins as potent and selective human β-secretase inhibitors is reported. These analogs exhibit good brain permeability (40-70%), low nanomolar potency for BACE1, and demonstrate >100-fold selectivity for the structurally related aspartyl proteases cathepsin D, renin and pepsin. Alkyl and alkoxy groups at the meta-position of the P1 phenyl, which extend toward the S3 region of the enzyme, have contributed to the ligand's reduced affinity for the efflux transporter protein P-gp, and decreased topological polar surface area, thus resulting in enhanced brain permeability. A fluorine substitution at the para-position of the P1 phenyl has contributed to 100-fold decrease of CYP3A4 inhibition and enhancement of compound metabolic stability. The plasma and brain protein binding properties of these new analogs are affected by substitutions at the P1 phenyl moiety. Higher compound protein binding was observed in the brain than in the plasma. Two structurally diverse potent BACE1 inhibitors (84 and 89) reduced 30% plasma Aβ40 in the Tg2576 mice in vivo model at 30 mg/kg p.o.. 相似文献
24.
Jose MG Vilar 《BMC systems biology》2010,4(1):152
Background
Cellular responses to death-promoting stimuli typically proceed through a differentiated multistage process, involving a lag phase, extensive death, and potential adaptation. Deregulation of this chain of events is at the root of many diseases. Improper adaptation is particularly important because it allows cell sub-populations to survive even in the continuous presence of death conditions, which results, among others, in the eventual failure of many targeted anticancer therapies. 相似文献25.
26.
Wills M Akbar A Beswick M Bosch JA Caruso C Colonna-Romano G Dutta A Franceschi C Fulop T Gkrania-Klotsas E Goronzy J Griffiths SJ Henson S Herndler-Brandstetter D Hill A Kern F Klenerman P Macallan D Macualay R Maier AB Mason G Melzer D Morgan M Moss P Nikolich-Zugich J Pachnio A Riddell N Roberts R Sansoni P Sauce D Sinclair J Solana R Strindhall J Trzonkowski P van Lier R Vescovini R Wang G Westendorp R Pawelec G 《Immunity & ageing : I & A》2011,8(1):10-8
The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion. 相似文献
27.
Alessandro S Guimarães Filipe B Carmo Marcos B Heinemann Ricardo WD Portela Roberto Meyer Andrey P Lage Núbia Seyffert Anderson Miyoshi Vasco Azevedo Aurora MG Gouveia 《BMC veterinary research》2011,7(1):1-5
Background
Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (PMEL17, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another horse breed, the Icelandic horse, which is historically quite divergent from Rocky Mountain horses.Results
We examined 24 Icelandic horses and established that the MCOA syndrome is present in this breed. Four of these horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the PMEL17 mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen horses were heterozygous for the PMEL17 mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional horses were genotyped as PMEL17 heterozygotes, but in these horses we were unable to detect cysts or other forms of anomalies. One eye of a severely vision-impaired 18 month-old stallion, homozygous for the PMEL17 mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen.Conclusions
The MCOA syndrome is segregating with the PMEL17 mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed. 相似文献28.
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