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161.
The genus Elminia has had a jumbled taxonomic history, being placed among ‘old world flycatchers’ or ‘monarch flycatchers’, where it was for a long time lumped with Trochocercus. It was recently suggested that it might represent a deep clade in the large sylvioid radiation. Using one mitochondrial protein‐coding gene (ND2, 1041 bp) and one nuclear intron (myoglobin intron 2, 700 bp) DNA sequences, we obtained robust evidence for the phylogenetic placement of Elminia in the new family Stenostiridae, which is strongly supported by a synapomorphic insertion of one base in the nuclear myoglobin intron 2 sequence. Our analyses confirm the monophyly of Elminia and resolve relationships within this genus, but cannot confidently identify its sister‐taxon within the stenostirid clade. Two clades were strongly supported within the genus Elminia: one with the two fairy blue flycatchers and another with the three white‐tailed crested‐flycatchers. Within the first clade, Elminia longicauda appears non‐monophyletic but remains strongly related to E. albicauda. In the second clade, E. albiventris is sister to E. albonotata while the Dusky Crested Flycatcher (E. nigromitrata) appears in a basal position within this clade. According to our molecular dating, several geological events in western Africa and the Albertine Rift area seem to be related to the historical distribution of Elminia. Thus, the differentiation between E. albonotata and E. albiventris could be directly related to the tectonic history of these two regions. According to our molecular dating, at least one intercontinental dispersal event involving Culicicapa took place within the Stenostiridae clade at a time when the Middle East was forested. 相似文献
162.
163.
Bourne C Roy S Wiley JL Martin BR Thomas BF Mahadevan A Razdan RK 《Bioorganic & medicinal chemistry》2007,15(24):7850-7864
The structure–activity relationship (SAR) of the end pentyl chain in anandamide (AEA) has been established to be very similar to that of Δ9-tetrahydrocannabinol (Δ9-THC). In order to broaden our understanding of the structural similarities between AEA and THC, hybrid structures 1–3 were designed. In these hybrids the aromatic ring of THC–DMH was linked to the AEA moiety through an ether linkage with the oxygen of the phenol of THC. Hybrid 1 (O-2220) was found to have very high binding affinity to CB1 receptors (Ki = 8.5 nM), and it is interesting to note that the orientation of the side chain with respect to the oxygen in the phenol is the same as in THCs. To further explore the SAR in this series the terminal carbon of the side chain was modified by adding different substituents. Several such analogs were synthesized and tested for their CB1 and CB2 binding affinities and in vivo activity (tetrad tests). The details of the synthesis and the biological activity of these compounds are described. 相似文献
164.
165.
Huffman JW Mabon R Wu MJ Lu J Hart R Hurst DP Reggio PH Wiley JL Martin BR 《Bioorganic & medicinal chemistry》2003,11(4):539-549
A series of 1-pentyl-1H-indol-3-yl-(1-naphthyl)methanes (9-11) and 2-methyl-1-pentyl-1H-indol-3-yl-(1-naphthyl)methanes (12-14) have been synthesized to investigate the hypothesis that cannabimimetic 3-(1-naphthoyl)indoles interact with the CB(1) receptor by hydrogen bonding to the carbonyl group. Indoles 9-11 have significant (K(i)=17-23nM) receptor affinity, somewhat less than that of the corresponding naphthoylindoles (5, 15, 16). 2-Methyl-1-indoles 12-14 have little affinity for the CB(1) receptor, in contrast to 2-methyl-3-(1-naphthoyl)indoles 17-19, which have affinities comparable to those of 5, 15, 16. A cannabimimetic indene hydrocarbon (26) was synthesized and found to have K(i)=26+/-4nM. Molecular modeling and receptor docking studies of naphthoylindole 16, its 2-methyl congener (19) and indolyl-1-naphthylmethanes 11 and 14, combined with the receptor affinities of these cannabimimetic indoles, strongly suggest that these cannabinoid receptor ligands bind primarily by aromatic stacking interactions in the transmembrane helix 3-4-5-6 region of the CB(1) receptor. 相似文献
166.
Brooke M. Steenhard Roberto Vanacore David Friedman Adrian Zelenchuk Larysa Stroganova Kathryn Isom Patricia L. St. John Billy G. Hudson Dale R. Abrahamson 《PloS one》2012,7(12)
Alport disease in humans, which usually results in proteinuria and kidney failure, is caused by mutations to the COL4A3, COL4A4, or COL4A5 genes, and absence of collagen α3α4α5(IV) networks found in mature kidney glomerular basement membrane (GBM). The Alport mouse harbors a deletion of the Col4a3 gene, which also results in the lack of GBM collagen α3α4α5(IV). This animal model shares many features with human Alport patients, including the retention of collagen α1α2α1(IV) in GBMs, effacement of podocyte foot processes, gradual loss of glomerular barrier properties, and progression to renal failure. To learn more about the pathogenesis of Alport disease, we undertook a discovery proteomics approach to identify proteins that were differentially expressed in glomeruli purified from Alport and wild-type mouse kidneys. Pairs of cy3- and cy5-labeled extracts from 5-week old Alport and wild-type glomeruli, respectively, underwent 2-dimensional difference gel electrophoresis. Differentially expressed proteins were digested with trypsin and prepared for mass spectrometry, peptide ion mapping/fingerprinting, and protein identification through database searching. The intermediate filament protein, vimentin, was upregulated ∼2.5 fold in Alport glomeruli compared to wild-type. Upregulation was confirmed by quantitative real time RT-PCR of isolated Alport glomeruli (5.4 fold over wild-type), and quantitative confocal immunofluorescence microscopy localized over-expressed vimentin specifically to Alport podocytes. We next hypothesized that increases in vimentin abundance might affect the basement membrane protein receptors, integrins, and screened Alport and wild-type glomeruli for expression of integrins likely to be the main receptors for GBM type IV collagen and laminin. Quantitative immunofluorescence showed an increase in integrin α1 expression in Alport mesangial cells and an increase in integrin α3 in Alport podocytes. We conclude that overexpression of mesangial integrin α1 and podocyte vimentin and integrin α3 may be important features of glomerular Alport disease, possibly affecting cell-signaling, cell shape and cellular adhesion to the GBM. 相似文献
167.
168.
Ghadami M El-Demerdash E Zhang D Salama SA Binhazim AA Archibong AE Chen X Ballard BR Sairam MR Al-Hendy A 《PloS one》2012,7(3):e32462
Recent studies suggest that bone marrow stem cells (BMSCs) are promising grafts to treat a variety of diseases, including reproductive dysfunction. Primary ovarian failure is characterized by amenorrhea and infertility in a normal karyotype female, with an elevated serum level of follicle-stimulating hormone (FSH) and a decrease level of estrogen caused by a mutation in FSH receptor (FSHR) gene. Currently, there is no effective treatment for this condition. The phenotype of FSHR (-/-) mouse, FORKO (follitropin receptor knockout), is a suitable model to study ovarian failure in humans. Female FORKO mice have elevated FSH, decreased estrogen levels, are sterile because of the absence of folliculogenesis, and display thin uteri and small nonfunctional ovaries. In this study, we determined the effects of BMSC transplantation on reproductive physiology in this animal model. Twenty four hours post BMSC transplantation, treated animals showed detectable estroidogeneic changes in daily vaginal smear. Significant increase in total body weight and reproductive organs was observed in treated animals. Hemotoxylin and eosin (H&E) evaluation of the ovaries demonstrated significant increase in both the maturation and the total number of the follicles in treated animals. The FSH dropped to 40-50% and estrogen increased 4-5.5 times in the serum of treated animals compared to controls. The FSHR mRNA was detected in the ovaries of treated animals. Our results show that intravenously injected BMSCs were able to reach the ovaries of FORKO mice, differentiate and express FHSR gene, make FSHR responsive to FSH, resume estrogen hormone production, and restore folliculogenesis. 相似文献
169.
Zhang H Chen GG Zhang Z Chun S Leung BC Lai PB 《Apoptosis : an international journal on programmed cell death》2012,17(4):325-334
SB203580 is a well-known inhibitor of p38 mitogen-activated protein kinase (MAPK). However, it can suppress cell proliferation
in a p38 MAPK independent manner. The inhibitory mechanism remains unknown. Here, we showed that SB203580 induced autophagy
in human hepatocellular carcinoma (HCC) cells. SB203580 increased GFP-LC3-positive cells with GFP-LC3 dots, induced accumulation
of autophagosomes, and elevated the levels of microtubule-associated protein light chain 3 and Beclin 1. It stimulated the
phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and p53, but inhibited the phosphorylation of death-associated
protein kinase (DAPK). Inhibition of AMPK, p53, or DAPK attenuated SB203580-induced autophagy. AMPK activation appeared to
predate the DAPK signal. The activation of both AMPK and DAPK prompted the phosphorylation of p53 and enhanced Beclin 1 expression.
Neither the downregulation of p38 MAPK by its siRNA or chemical inhibitor nor the upregulation of p38 MAPK by p38 MAPK DNA
transfection affected B203580-induced autophagy. Collectively, the findings demonstrate a novel function of SB203580 to induce
autophagy via activating AMPK and DAPK but independent of p38 MAPK. The induction of autophagy can thus account for the antiproliferative
effect of SB203580 in HCC cells. 相似文献
170.
Abair TD Sundaramoorthy M Chen D Heino J Ivaska J Hudson BG Sanders CR Pozzi A Zent R 《Experimental cell research》2008,314(19):3593-3604
The collagen-binding integrins α1β1 and α2β1 have profoundly different functions, yet they are often co-expressed in epithelial cells. When both integrins are expressed in the same cell, it has been suggested that α1β1 negatively regulates integrin α2β1-dependent functions. In this study we utilized murine ureteric bud (UB) epithelial cells, which express no functionally detectable levels of endogenous integrins α1β1 and α2β1, to determine the mechanism whereby this regulation occurs. We demonstrate that UB cells expressing integrin α2β1, but not α1β1 adhere, migrate and proliferate on collagen I as well as form cellular cords in 3D collagen I gels. Substitution of the transmembrane domain of the integrin α2 subunit with that of α1 results in decreased cell adhesion, migration and cord formation. In contrast, substitution of the integrin α2 cytoplasmic tail with that of α1, decreases cell migration and cord formation, but increases proliferation. When integrin α1 and α2 subunits are co-expressed in UB cells, the α1 subunit negatively regulates integrin α2β1-dependent cord formation, adhesion and migration and this inhibition requires expression of both α1 and α2 tails. Thus, we provide evidence that the transmembrane and cytoplasmic domains of the α2 integrin subunit, as well as the α1 integrin subunit, regulate integrin α2β1 cell function. 相似文献