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31.
Metabolite-dependent conformational switching in RNA riboswitches is now widely accepted as a critical regulatory mechanism for gene expression in bacterial systems. More recently, similar gene regulation mechanisms have been found to be important for viral systems as well. One of the most abundant and best-studied systems is the tRNA-like structure (TLS) domain, which has been found to occur in many plant viruses spread across numerous genera. In this work, folding dynamics for the TLS domain of Brome Mosaic Virus have been investigated using single-molecule fluorescence resonance energy transfer techniques. In particular, burst fluorescence methods are exploited to observe metal-ion ([Mn+])-induced folding in freely diffusing RNA constructs resembling the minimal TLS element of brome mosaic virus RNA3. The results of these experiments reveal a complex equilibrium of at least three distinct populations. A stepwise, or consecutive, thermodynamic model for TLS folding is developed, which is in good agreement with the [Mn+]-dependent evolution of conformational populations and existing structural information in the literature. Specifically, this folding pathway explains the metal-ion dependent formation of a functional TLS domain from unfolded RNAs via two consecutive steps: 1) hybridization of a long-range stem interaction, followed by 2) formation of a 3′-terminal pseudoknot. These two conformational transitions are well described by stepwise dissociation constants for [Mg2+] (K1 = 328 ± 30 μM and K2 = 1092 ± 183 μM) and [Na+] (K1 = 74 ± 6 mM and K2 = 243 ± 52 mM)-induced folding. The proposed thermodynamic model is further supported by inhibition studies of the long-range stem interaction using a complementary DNA oligomer, which effectively shifts the dynamic equilibrium toward the unfolded conformation. Implications of this multistep conformational folding mechanism are discussed with regard to regulation of virus replication. 相似文献
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Emma Tham Anna Lindstrand Avni Santani Helena Malmgren Addie Nesbitt Holly?A. Dubbs Elaine?H. Zackai Michael?J. Parker Francisca Millan Kenneth Rosenbaum Golder?N. Wilson Ann Nordgren 《American journal of human genetics》2015,96(3):507-513
Through a multi-center collaboration study, we here report six individuals from five unrelated families, with mutations in KAT6A/MOZ detected by whole-exome sequencing. All five different de novo heterozygous truncating mutations were located in the C-terminal transactivation domain of KAT6A: : c.3116_3117 delCT, p.(Ser1039∗); c.3830_3831insTT, p.(Arg1278Serfs∗17); c.3879 dupA, p.(Glu1294Argfs∗19); c.4108G>T p.(Glu1370∗) and c.4292 dupT, p.(Leu1431Phefs∗8). An additional subject with a 0.23 MB microdeletion including the entire KAT6A reading frame was identified with genome-wide array comparative genomic hybridization. Finally, by detailed clinical characterization we provide evidence that heterozygous mutations in KAT6A cause a distinct intellectual disability syndrome. The common phenotype includes hypotonia, intellectual disability, early feeding and oromotor difficulties, microcephaly and/or craniosynostosis, and cardiac defects in combination with subtle facial features such as bitemporal narrowing, broad nasal tip, thin upper lip, posteriorly rotated or low-set ears, and microretrognathia. The identification of human subjects complements previous work from mice and zebrafish where knockouts of Kat6a/kat6a lead to developmental defects. NM_001099412.1相似文献
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In the rainfed lowlands, temporary loss of soil-water saturation during crop growth is a common factor limiting rice (Oryza
sativa L.) yield but its effects on phosphorus (P) availability are poorly understood. Rice plants were transplanted into
pots containing soils that were either continuously flooded, maintained at field capacity or flooded and then dried to field
capacity for 3 weeks during the vegetative stage. A black clay soil (Kandic Plinthaquult) and a sandy soil (Plinthustalf)
from south-east Cambodia were compared with or without amendments by rice straw and P fertilizer.
Under continuously flooded conditions, the growth of rice was vigorous without straw addition and there was a strong response
of rice growth to the addition of P fertilizer. The soil underwent reduction, which increased pH from 4.2 to 5.5 or 6.0, in
the black clay or sandy soil, respectively. By contrast, a loss of soil-water saturation 3 weeks before panicle initiation
(PI) markedly impaired the growth of rice. This was not through any effect of water stress, and the growth reductions were
not as strong as with continued loss of soil-water saturation from transplanting to PI. Fluctuations in soil pH and Eh corresponded
closely to changes in soil-water regimes. Growth reductions were attributed to reduced shoot P levels resulting from the decline
in P availability during the loss of soil-water saturation. The addition of rice straw stimulated soil reduction and lessened
changes in soil pH and Eh during the loss of soil-water saturation in both soils. Straw addition enhanced P uptake by the
rice plants during loss of soil-water saturation, but its beneficial effects could not be attributed to the direct addition
of P, N or K to the soils. Thus the application of rice straw may be effective in lessening the effects of temporary loss
of soil-water saturation on rice growth in lowland rice soils by minimising the decline in P availability.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
36.
Bente Christiansen Jens Pete Lomholt Kjell Johansen 《Environmental Biology of Fishes》1982,7(3):291-296
Synopsis Oxygen uptake (Vo
2) was measured in carp of approximately 40 cm length swimming at controlled variable oxygen tensions (Po
2). At Po
2> 120 mm Hg Vo
2 increased with an increase in swimming speed from 5.6 to 11.3 cm · sec–1. Extrapolation of Vo
2 to zero activity at Po
2 = 140 mm Hg revealed a standard O2 uptake of 36.7 ml O2 · kg–1 · h–1 at 20° C. At the lowest swimming speed (5.6 cm · s–1) the oxygen uptake increased when the water Po
2 was reduced. A near doubling in Vo
2 was seen at Po
2 = 70 mm Hg compared to 140 mm Hg. At higher swimming speeds in hypoxic water Vo
2 decreased relative to the values at low swimming speeds. As a result the slope of the lines expressing log Vo
2 as a function of swimming speed decreased from positive to negative values with decreasing Po
2 of the water. pH of blood from the caudal vein drawn before and at termination of swimming at Po
2 = 70 mm Hg and 100 mm Hg did not show any decrease in relation to rest values at Po
2 = 140 mm Hg. Blood lactate concentration did not increase during swimming at these tensions. 相似文献
37.
Peleg Leah Nesbitt Muriel N. Ashkenazi Israel E. 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1982,147(1):137-142
Journal of Comparative Physiology A - A/J mice differ from C57BL/6J mice in the time of the daily peak of activity of glyceraldehyde-3-phosphate dehydrogenase (GAPD) in thymus and in thyroid.... 相似文献
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Ruth R. Miller Miguel Uyaguari-Diaz Mark N. McCabe Vincent Montoya Jennifer L. Gardy Shoshana Parker Theodore Steiner William Hsiao Matthew J. Nesbitt Patrick Tang David M. Patrick for the CCD Study Group 《PloS one》2016,11(11)
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease causing indefinite fatigue. ME/CFS has long been hypothesised to have an infectious cause; however, no specific infectious agent has been identified. We used metagenomics to analyse the RNA from plasma samples from 25 individuals with ME/CFS and compare their microbial content to technical controls as well as three control groups: individuals with alternatively diagnosed chronic Lyme syndrome (N = 13), systemic lupus erythematosus (N = 11), and healthy controls (N = 25). We found that the majority of sequencing reads were removed during host subtraction, thus there was very low microbial RNA content in the plasma. The effects of sample batching and contamination during sample processing proved to outweigh the effects of study group on microbial RNA content, as the few differences in bacterial or viral RNA abundance we did observe between study groups were most likely caused by contamination and batch effects. Our results highlight the importance of including negative controls in all metagenomic analyses, since there was considerable overlap between bacterial content identified in study samples and control samples. For example, Proteobacteria, Firmicutes, Actinobacteria, and Bacteriodes were found in both study samples and plasma-free negative controls. Many of the taxonomic groups we saw in our plasma-free negative control samples have previously been associated with diseases, including ME/CFS, demonstrating how incorrect conclusions may arise if controls are not used and batch effects not accounted for. 相似文献