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51.
Yeast mitochondrial initiator tRNA is methylated at guanosine 37 by the Trm5-encoded tRNA (guanine-N1-)-methyltransferase 总被引:2,自引:0,他引:2
The TRM5 gene encodes a tRNA (guanine-N1-)-methyltransferase (Trm5p) that methylates guanosine at position 37 (m(1)G37) in cytoplasmic tRNAs in Saccharomyces cerevisiae. Here we show that Trm5p is also responsible for m(1)G37 methylation of mitochondrial tRNAs. The TRM5 open reading frame encodes 499 amino acids containing four potential initiator codons within the first 48 codons. Full-length Trm5p, purified as a fusion protein with maltose-binding protein, exhibited robust methyltransferase activity with tRNA isolated from a Delta trm5 mutant strain, as well as with a synthetic mitochondrial initiator tRNA (tRNA(Met)(f)). Primer extension demonstrated that the site of methylation was guanosine 37 in both mitochondrial tRNA(Met)(f) and tRNA(Phe). High pressure liquid chromatography analysis showed the methylated product to be m(1)G. Subcellular fractionation and immunoblotting of a strain expressing a green fluorescent protein-tagged version of the TRM5 gene revealed that the enzyme was localized to both cytoplasm and mitochondria. The slightly larger mitochondrial form was protected from protease digestion, indicating a matrix localization. Analysis of N-terminal truncation mutants revealed that a Trm5p active in the cytoplasm could be obtained with a construct lacking amino acids 1-33 (Delta1-33), whereas production of a Trm5p active in the mitochondria required these first 33 amino acids. Yeast expressing the Delta1-33 construct exhibited a significantly lower rate of oxygen consumption, indicating that efficiency or accuracy of mitochondrial protein synthesis is decreased in cells lacking m(1)G37 methylation of mitochondrial tRNAs. These data suggest that this tRNA modification plays an important role in reading frame maintenance in mitochondrial protein synthesis. 相似文献
52.
Oswaldo Hernández-Gallegos Gisela Granados-González Justin L. Rheubert Maricela Villagrán-SantaCruz Eric Peña-Herrera Kevin M. Gribbins 《Acta zoologica》2019,100(4):359-364
Although different mechanisms exist to explain the presence of polymorphism in lizards, one model suggests that multiple morphotypes display the same level of fitness. Three male morphs (grey, yellow and orange) coexist in Sceloporus aeneus, a Mexican endemic oviparous lizard. Using a histological perspective, we test the hypothesis that spermatogenic output does not vary across morphotypes of S. aeneus during its maximum testicular activity. Males of S. aeneus (five grey, five yellow and five orange) were collected in Calimaya, Estado de México, Mexico. Snout-vent length (SVL), testis mass, diameter and epithelial heights for the seminiferous tubules and epididymis, and the number of layers of germ cells did not vary among morphs; moreover, according to principal component analysis, a high overlap among lateral colour morphs exists. Our results suggest strongly that the lateral colour morphs in S. aeneus have the same spermatogenic output, and natural selection may be a stronger driving force than sexual selection within this species. Further studies into other lizard species with multiple morphotypes are required to determine whether the lack of variation in spermatogenic output observed in this endemic lizard is consistent across polymorphic species which will provide a greater understanding of the selective mechanisms acting on an individual’s fitness. 相似文献
53.
Gisela Granados-González Maricela Villagrán-SantaCruz Eric Peña-Herrera Justin L. Rheubert Kevin M. Gribbins Oswaldo Hernández-Gallegos 《Acta zoologica》2019,100(1):43-52
Gaining a deeper understanding of spermatogenic cycles within squamates has aided in our knowledge of the controls of reproduction and has bettered our understanding of reproductive phenology. One of the most studied genera of squamates, Sceloporus, is widely distributed along a latitudinal and elevational gradient in temperate, tropical, low-elevation and high-elevation habitats. Due to this wide distribution and varying habitats, Sceloporus exhibit differences in their spermatogenic activity (including both cyclical and acyclical patterns) and may be one of the most useful genera for understanding the abiotic correlations with spermatogenesis. The spermatogenic activity in Sceloporus variabilis was studied histologically (in a population that inhabits a tropical region at Los Tuxtlas, Veracruz, Mexico) and found to exhibit a unique cyclical pattern with an extended period of maximum activity (from November to July) and the absence of regression and quiescence. Furthermore, these data corroborate previous works on the spermatogenic cycles of S. variabilis despite different populations utilised. These data suggest that although abiotic factors may play a role in the timing of spermatogenesis, phylogenetic signal may be equally as important. More data concerning spermatogenic cycles in phylogenetically related taxa from differing habitats will elucidate the patterns of spermatogenic diversity. 相似文献
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Pey R Bach J Schieren G Gretz N Hafner M 《In vitro cellular & developmental biology. Animal》1999,35(10):571-579
Summary Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent human inherited diseases. The main feature
of the disease is the development of renal cysts, first occurring in the proximal tubules, and with time, dominating all segments
of the nephron, leading to end-stage renal disease in 50% of the patients in their fifth decade of life. A therapy for polycystic
kidney disease (PKD) has not yet been developed. Patients coming to end-stage ADPKD require long-term dialysis and/or transplantation.
A suitable animal model to study ADPKD is the spontaneously mutated Han:SPRD (cy/ +) rat, but a method to cultivate Han:SPRD (cy/ +) derived renal cells which preserves their ability to form cyst-like structures in vitro has previously not been reported.
Based on this well-characterized animal model, we developed a cell culture model of renal cyst formation in vitro. When renal
cells of the Han:SPRD (cy/ +) rat were isolated and cultured under conditions that prevent cell-substratum adhesion, large amounts of cyst-like structures
were formed de novo from Han:SPRD (cy/ +) derived renal cells, but only a few from control rat renal cells. In contrast, when cultivated on plastic as monolayer
cultures, Han:SPRD (cy/ +)-derived and control rat-derived renal cells were indistinguishable and did not form cyst-like structures. Immunohistochemical
characterization of the cyst-like structures suggests tubular epithelial origin of the cyst-forming cells. The amount of cysts
formed from Han:SPRD (cy/ +)-derived renal cells grown in a stationary suspension culture is susceptible to modulation by different conditions. Human
cyst fluid and epidermal growth factor both stimulated the formation of cysts from Han:SPRD (cy/ +)-derived renal cells whereas taxol inhibited cystogenesis. In contrast, neither human cyst fluid nor epidermal growth
factor affected the amount of cysts formed by control rat renal cells. As the culture model reported here allows not only
the distinction of PKD-derived tubular epithelium from its normal counterpart, but also the modulation of cyst formation especially
by Han:SPRD (cy/ +)-derived renal cells, it might be a useful prescreening protocol for potential treatments for PKD and thus reduce the
need for animal experiments.
Both authors contributed equally to the work. 相似文献
57.
Zhou HM Weskamp G Chesneau V Sahin U Vortkamp A Horiuchi K Chiusaroli R Hahn R Wilkes D Fisher P Baron R Manova K Basson CT Hempstead B Blobel CP 《Molecular and cellular biology》2004,24(1):96-104
Congenital heart disease is the most common form of human birth defects, yet much remains to be learned about its underlying causes. Here we report that mice lacking functional ADAM19 (mnemonic for a disintegrin and metalloprotease 19) exhibit severe defects in cardiac morphogenesis, including a ventricular septal defect (VSD), abnormal formation of the aortic and pulmonic valves, leading to valvular stenosis, and abnormalities of the cardiac vasculature. During mouse development, ADAM19 is highly expressed in the conotruncus and the endocardial cushion, structures that give rise to the affected heart valves and the membranous ventricular septum. ADAM19 is also highly expressed in osteoblast-like cells in the bone, yet it does not appear to be essential for bone growth and skeletal development. Most adam19(-/-) animals die perinatally, likely as a result of their cardiac defects. These findings raise the possibility that mutations in ADAM19 may contribute to human congenital heart valve and septal defects. 相似文献
58.
Smith G Ruhland T Mikkelsen G Andersen K Christoffersen CT Alifrangis LH Mørk A Wren SP Harris N Wyman BM Brandt G 《Bioorganic & medicinal chemistry letters》2004,14(15):4027-4030
Elevation of glycine levels and activation of the NMDA receptor by inhibition of the glycine transporter 1 (GlyT-1) is a potential strategy for the treatment of schizophrenia. A novel series of GlyT-1 inhibitors have been identified containing the 2-arylsulfanyl-phenylpiperazine motif. The most prominent member of this series, (R)-4-[5-chloro-2-(4-methoxy-phenylsulfanyl)-phenyl]-2-methyl-piperazin-1-yl-acetic acid (31) is a potent glycine transporter-1 inhibitor (IC(50)=150 nM), which elevated glycine levels in rat ventral hippocampus as measured by microdialysis in vivo at doses of 1.2-4.6 mg/kg s.c. 相似文献
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60.
Tubio G Nerli B Picó G 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,799(2):293-301
In order to develop possible correlations to predict partioning behaviour of proteins, five mammalian albumins (goat, bovine, equine, human and pig ones) with similar physico-chemical properties (molecular mass and isoelectrical point) were chosen. Evaluation of the relationship between hydrophobicity and partitioning coefficient (Kr) in polyethylenglycol-dextran (PEG-DxT500) systems formed by polyethyleneglycols of different molecular mass (3350, 6000 and 10,000) was investigated by estimating relative surface hydrophobicity (So) with a fluorescent probe, 1 anilino-8-naphthalene sulfonate. No relationship between Kr and So was found for systems formed by PEG3350, while aqueous two-phase systems with PEG6000 and PEG10,000 gave better correlations. The results obtained may be explained on the basis of an increase in the interaction between the latter PEGs and the protein due to their higher hydrophobic character which increases as the PEG molecular mass does so. In this way, systems with PEGs of higher molecular mass give the highest resolution to exploit hydrophobicity in partitioning. 相似文献