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21.
22.
Inspiratory muscle weakness in patients with COPD is of major clinical relevance. For instance, maximum inspiratory pressure generation is an independent determinant of survival in severe COPD. Traditionally, inspiratory muscle weakness has been ascribed to hyperinflation-induced diaphragm shortening. However, more recently, invasive evaluation of diaphragm contractile function, structure, and biochemistry demonstrated that cellular and molecular alterations occur, of which several can be considered pathologic of nature. Whereas the fiber type shift towards oxidative type I fibers in COPD diaphragm is regarded beneficial, rendering the overloaded diaphragm more resistant to fatigue, the reduction of diaphragm fiber force generation in vitro likely contributes to diaphragm weakness. The reduced diaphragm force generation at single fiber level is associated with loss of myosin content in these fibers. Moreover, the diaphragm in COPD is exposed to oxidative stress and sarcomeric injury. This review postulates that the oxidative stress and sarcomeric injury activate proteolytic machinery, leading to contractile protein wasting and, consequently, loss of force generating capacity of diaphragm fibers in patients with COPD. Interestingly, several of these presumed pathologic alterations are already present early in the course of the disease (GOLD I/II), although these patients appear not limited in their daily life activities. Treatment of diaphragm dysfunction in COPD is complex since its etiology is unclear, but recent findings indicate the ubiquitin-proteasome pathway as a prime target to attenuate diaphragm wasting in COPD. 相似文献
23.
Phillip Q Spinks Robert C Thomson Geoff A Lovely H Bradley Shaffer 《BMC evolutionary biology》2009,9(1):1-17
Background
Section Calochroi is one of the most species-rich lineages in the genus Cortinarius (Agaricales, Basidiomycota) and is widely distributed across boreo-nemoral areas, with some extensions into meridional zones. Previous phylogenetic studies of Calochroi (incl. section Fulvi) have been geographically restricted; therefore, phylogenetic and biogeographic relationships within this lineage at a global scale have been largely unknown. In this study, we obtained DNA sequences from a nearly complete taxon sampling of known species from Europe, Central America and North America. We inferred intra- and interspecific phylogenetic relationships as well as major morphological evolutionary trends within section Calochroi based on 576 ITS sequences, 230 ITS + 5.8S + D1/D2 sequences, and a combined dataset of ITS + 5.8S + D1/D2 and RPB1 sequences of a representative subsampling of 58 species. 相似文献24.
Determining the quality and complexity of next-generation sequencing data without a reference genome
Seyed Yahya Anvar Lusine Khachatryan Martijn Vermaat Michiel van Galen Irina Pulyakhina Yavuz Ariyurek Ken Kraaijeveld Johan T den Dunnen Peter de Knijff Peter AC ’t Hoen Jeroen FJ Laros 《Genome biology》2014,15(12)
We describe an open-source kPAL package that facilitates an alignment-free assessment of the quality and comparability of sequencing datasets by analyzing k-mer frequencies. We show that kPAL can detect technical artefacts such as high duplication rates, library chimeras, contamination and differences in library preparation protocols. kPAL also successfully captures the complexity and diversity of microbiomes and provides a powerful means to study changes in microbial communities. Together, these features make kPAL an attractive and broadly applicable tool to determine the quality and comparability of sequence libraries even in the absence of a reference sequence. kPAL is freely available at https://github.com/LUMC/kPAL.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0555-3) contains supplementary material, which is available to authorized users. 相似文献25.
26.
This study utilized the transfer of preimplantation embryos to pseudo-pregnant mice to determine whether PAF-antagonists act primarily on the maternal or embryonic components of implantation. The first experiment used reciprocal embryo transfers, in which blastocysts from mice treated with PAF antagonist (SRI 63-441) or saline (controls), from Days 1 to 4 of pregnancy, were transferred to Day-3 pseudo-pregnant recipients which were also treated with SRI 63-441 or saline on Days 1-4 of pregnancy. The antagonist (40 micrograms) was administered at 16:00 h on Day 1 and at 09:00 h on Days 2-4 of pregnancy. The percentage of the transferred embryos which implanted was determined on Day 8 of pregnancy. Treatment of the recipient or the donor female with SRI 63-441 resulted in a reduction in implantation rate, from a control level of 45% to 33.8% or 34.7% (P less than 0.0002, P less than 0.007) respectively. These results suggest that the PAF antagonist affected implantation at the embryonic and maternal levels. However, when the blastocysts were transferred to Day-4 pseudopregnant recipients, treatment of the donor female had a dramatic effect on the implantation rate, resulting in a reduction of 64% (from 40% to 14.3%, P less than 0.04), while treatment of the recipient female had no significant effect. In this later experiment the transferred embryos were exposed to the recipient uterine environment for a shorter period before implantation. These results suggest that PAF antagonists affected implantation at the embryonic level and did not adversely affect maternal physiology.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
27.
Implantation potential and fetal viability of mouse embryos cultured in media supplemented with platelet-activating factor 总被引:7,自引:0,他引:7
Supplementation of culture media with PAF failed to increase the proportion of 2-cell mouse embryos which developed through to the expanded blastocyst stage after 72 h of culture in vitro. Culture of embryos with 1.86 microM-PAF, however, significantly increased the number of cells in expanded blastocysts. Culture in vitro with 0.186 or 1.86 microM-PAF significantly increased the ability of embryos to implant upon transfer to pseudopregnant recipients. The specificity of this effect was demonstrated by its inhibition by the specific PAF-receptor antagonist, SRI 63-441. Of the embryos which implanted, there was no difference in the proportions of PAF-treated or control embryos which resorbed nor was there any effect of PAF on fetal weight or crown-rump length measurements. Embryos cultured with 1.86 microM-PAF did have slightly heavier placentae than their respective controls. These results demonstrate the ability of exogenous PAF to enhance the viability of preimplantation mouse embryos cultured in vitro and support the hypothesis that a major site of the action of PAF during early pregnancy is the embryo itself. 相似文献
28.
We investigated some of the ecological determinants of sociality in the Damaraland mole-rat, including the spatial distribution
and biomass of resources (geophytes) available to foraging Damaraland mole-rats in partly vegetated sand dunes in the Kalahari
and in grasslands near Dordabis, Namibia, and the foraging behaviour and residency characteristics of colonies at Dordabis.
In both study areas, the geophytes had a clumped distribution, but the highest coefficients of dispersion and mean biomass
occurred in the Kalahari where the principal food was the gemsbok cucumber. However, because the coefficient of digestibility
was lower in geophytes from the Kalahari than from Dordabis, and the mole-rats only ate about half of a gemsbok cucumber,
there was less energy available to mole-rats in the Kalahari. At Dordabis, large established colonies occur in the areas with
the richest resources and remain resident in the same area for many years; within this area they search (blindly) for food
during brief periods when the soil, at burrow depth, is moist and easily worked. Initially, long straight burrows are dug
and few bulbs are taken; once the soil dries, minor changes are made to the burrow system as the mole-rats exploit the food
patches they located immediately after the rain. Our results show that the characteristics of the resources, and the short
time interval during which location of new resources is possible, favour group living; however, the constraints imposed by
these features affect large and small colonies in different ways. Small colonies are more likely to fail than large ones and
some crucial factors in the survival of these newly formed colonies are the richness of the area in which their burrows are
located, and the size of the colony work force available to locate the food.
Received: 6 May 1997 / Accepted: 21 August 1997 相似文献
29.
Asian box turtles (genus Cuora, family Geoemydidae) comprise a clade of 12 aquatic and semiaquatic nominate species distributed across southern China and
Southeast Asia. Over the last two decades, turtles throughout Asia have been harvested at an unsustainable rate to satisfy
demands for food, traditional Chinese medicine, and the pet trade. Consequently, all species of Cuora were recently placed on the IUCN Red List, nine are currently listed as critically endangered by the IUCN, and all species
are listed in Appendix II of CITES. We compiled a 67-specimen mitochondrial (∼1,650 base pairs (bp) from two mitochondrial
genes) and a 40-specimen nuclear-plus-mitochondrial (∼3,900 bp total, three nuclear introns plus an additional ∼860 bp mitochondrial
gene fragment) DNA data set to reconstruct the phylogeny of Cuora species and to assess genetic diversity and species boundaries for several of the most problematic taxa. Our sampling included
23 C. trifasciata, 17 C. zhoui and 1–4 individuals of the remaining 10 species of Cuora. Maximum likelihood, maximum parsimony and Bayesian analyses all recovered similar, well resolved trees. Within the Cuora clade, mitochondrial and nuclear sequence data indicated that both C. zhoui and C. mccordi represent old lineages with little or no history of interspecific gene flow, suggesting that they are good genealogical species.
Based on mtDNA, Cuora pani was paraphyletic and C. trifasciata was composed of two highly divergent lineages that were not each other’s closest relatives; both cases of non-monophyly were
due to a mtDNA sequence that was widespread and identical in C. aurocapitata, C. pani and C. trifasciata. However, when combined with nuclear DNA results, our data indicate that C. trifasciata is a single, monophyletic taxon, and that mitochondrial introgression and nuclear-mitochondrial pseudogenes have led to a
complex pattern of mitochondrial gene relationships that does not reflect species-level histories. Our results imply that
captive “assurance colonies” of both C. trifasciata and C. pani should be genotyped to identify pure, non-hybrid members of both taxa, and we recommend that introgressed and pure taxa be
managed as independent entities until the full evolutionary histories of these critically endangered turtles are resolved. 相似文献
30.
Mark Reid Ian Carlyle Wilson L. Caulfield Tom R. Clarkson Fiona Cusick Ola Epemolu Robert Gilfillan Richard Goodwin David Jaap Elise C. O’Donnell Jeremy Presland Zoran Rankovic Daniel Spinks Gayle Spinks Anne M. Thomson Fiona Thomson James Strain Grant Wishart 《Bioorganic & medicinal chemistry letters》2010,20(12):3713-3716
Antagonists of the 5-HT6 receptor have been shown to improve cognitive function in a wide range of animal models and as such may prove to be attractive agents for the symptomatic treatment of cognitive disorders such as Alzheimer’s disease (AD) and schizophrenia. We report herein the identification and SAR around N-(2-aminoalkyl)-1-(arylsulfonyl)indoline-3-carboxamides—a novel chemotype of 5-HT6 antagonists. 相似文献