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31.
A rapid, sensitive high-performance liquid chromatography assay with fluorescence detection for measuring biphenyl metabolism by intact cells has been developed. The assay does not require organic solvent extraction or enzymatic digestion for the measurement of hydroxybiphenyl conjugates. The lower limit of detectability for 4-hydroxybiphenyl is 5 pmol injected. Rat hepatocytes incubated with biphenyl form predominantly 4-hydroxybiphenyl sulfate with lesser amounts of 4-hydroxybiphenyl glucuronide and free hydroxybiphenyls, and small amounts of 3-hydroxybiphenyl sulfate and 3-hydroxybiphenyl glucuronide. Slices of fresh human liver incubated with biphenyl form predominantly 4-hydroxybiphenyl glucuronide with some free hydroxybiphenyl and small amounts of 4-hydroxybiphenyl sulfate. 4-Hydroxybiphenyl glucuronide formation by human liver shows a lag time that is not abolished by preincubating the liver without substrate. Human kidney slices incubated with biphenyl form 4-hydroxybiphenyl glucuronide and 4-hydroxybiphenyl sulfate at rates less than one-tenth those seen with human liver. Human kidney slices do not form detectable free hydroxybiphenyl. There is wide intersubject variability in the rates of hydroxybiphenyl metabolite formation by human liver and kidney. 相似文献
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33.
Application of ultrasound for pregnancy diagnosis has been tested and evaluated in 15 Iranian camels (Camelus dromedarius), all of which ultimately calved. Transabdominal examinations were unsuccessful, while intrapelvic application resulted in the reception of sounds characteristic for foetal life, similar to those found in other domestic animals. Signals of foetal heart, pulse of umbilical vessels and uterine artery as well as foetal movement could be recognized as distinct sounds and have been recorded for further studies. An attempt was made to verify the findings of the ultrasonic diagnosis through rectal palpation. The ultrasonic technique resulted in 12 correct and three incorrect diagnoses. 相似文献
34.
Ribosomal protein S14 genes (RPS14) in eukaryotic species from protozoa to
primates exhibit dramatically different intron-exon structures yet share
homologous polypeptide-coding sequences. To recognize common features of
RPS14 gene architectures in closely related mammalian species and to
evaluate similarities in their noncoding DNA sequences, we isolated the
intron-containing S14 locus from Chinese hamster ovary (CHO) cell DNA by
using a PCR strategy and compared it with human RPS14. We found that rodent
and primate S14 genes are composed of identical protein-coding exons
interrupted by introns at four conserved DNA sites. However, the structures
of corresponding CHO and human RPS14 introns differ significantly.
Nonetheless, individual intron splice donor, splice acceptor, and upstream
flanking motifs have been conserved within mammalian S14 homologues as well
as within RPS14 gene fragments PCR amplified from other vertebrate genera
(birds and bony fish). Our data indicate that noncoding, intronic DNA
sequences within highly conserved, single-copy ribosomal protein genes are
useful molecular landmarks for phylogenetic analysis of closely related
vertebrate species.
相似文献
35.
George?M?WarimweEmail author Gema?Lorenzo Elena?Lopez-Gil Arturo?Reyes-Sandoval Matthew?G?Cottingham Alexandra?J?Spencer Katharine?A?Collins Matthew?DJ?Dicks Anita?Milicic Amar?Lall Julie?Furze Alison?V?Turner Adrian?VS?Hill Alejandro?Brun Sarah?C?Gilbert 《Virology journal》2013,10(1):349
Background
Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens.Methods
Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice.Results
A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response.Conclusions
Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.36.
37.
Andrew C Doxey Daniel A Kurtz Michael DJ Lynch Laura A Sauder Josh D Neufeld 《The ISME journal》2015,9(2):461-471
Cobalamin (vitamin B12) is a complex metabolite and essential cofactor required by many branches of life, including most eukaryotic phytoplankton. Algae and other cobalamin auxotrophs rely on environmental cobalamin supplied from a relatively small set of cobalamin-producing prokaryotic taxa. Although several Bacteria have been implicated in cobalamin biosynthesis and associated with algal symbiosis, the involvement of Archaea in cobalamin production is poorly understood, especially with respect to the Thaumarchaeota. Based on the detection of cobalamin synthesis genes in available thaumarchaeotal genomes, we hypothesized that Thaumarchaeota, which are ubiquitous and abundant in aquatic environments, have an important role in cobalamin biosynthesis within global aquatic ecosystems. To test this hypothesis, we examined cobalamin synthesis genes across sequenced thaumarchaeotal genomes and 430 metagenomes from a diverse range of marine, freshwater and hypersaline environments. Our analysis demonstrates that all available thaumarchaeotal genomes possess cobalamin synthesis genes, predominantly from the anaerobic pathway, suggesting widespread genetic capacity for cobalamin synthesis. Furthermore, although bacterial cobalamin genes dominated most surface marine metagenomes, thaumarchaeotal cobalamin genes dominated metagenomes from polar marine environments, increased with depth in marine water columns, and displayed seasonality, with increased winter abundance observed in time-series datasets (e.g., L4 surface water in the English Channel). Our results also suggest niche partitioning between thaumarchaeotal and cyanobacterial ribosomal and cobalamin synthesis genes across all metagenomic datasets analyzed. These results provide strong evidence for specific biogeographical distributions of thaumarchaeotal cobalamin genes, expanding our understanding of the global biogeochemical roles played by Thaumarchaeota in aquatic environments. 相似文献
38.
Kap-Sun Yeung Zhilei Qiu Zhiwei Yin Ashok Trehan Haiquan Fang Bradley Pearce Zheng Yang Lisa Zadjura Celia J. D’Arienzo Keith Riccardi Pei-Yong Shi Timothy P. Spicer Yi-Fei Gong Marc R. Browning Steven Hansel Kenneth Santone Jonathan Barker Thomas Coulter John F. Kadow 《Bioorganic & medicinal chemistry letters》2013,23(1):203-208
As part of the SAR profiling of the indole-oxoacetic piperazinyl benzamide class of HIV-1 attachment inhibitors, substitution at the C7 position of the lead 4-fluoroindole 2 with various 5- and 6-membered heteroaryl moieties was explored. Highly potent (picomolar) inhibitors of pseudotyped HIV-1 in a primary, cell-based assay were identified and select examples were shown to possess nanomolar inhibitory activity against M- and T-tropic viruses in cell culture. These C7-heteroaryl-indole analogs maintained the ligand efficiency (LE) of 2 and were also lipophilic efficient as measured by LLE and LELP. Pharmacokinetic studies of this class of inhibitor in rats showed that several possessed substantially improved IV clearance and half-lives compared to 2. Oral exposure in the rat correlated with membrane permeability as measured in a Caco-2 assay where the highly permeable 1,2,4-oxadiazole analog 13 exhibited the highest exposure. 相似文献
39.
Dolci S Belmonte A Santone R Giorgi M Pellegrini M Carosa E Piccione E Lenzi A Jannini EA 《Biochemical and biophysical research communications》2006,341(3):837-846
We investigated the subcellular localization of PDE5 in in vitro human myometrial cells. We demonstrated for the first time that PDE5 is localized in discrete cytoplasmic foci and vesicular compartments corresponding to centrosomes. We also found that PDE5 intracellular localization is not cell- or species-specific, as it is conserved in different animal and human cells. PDE5 protein levels are strongly regulated by the mitotic activity of the smooth muscle cells (SMCs), as they were increased in quiescent, contractile myometrial cultures, and conditions in which proliferation was inhibited. In contrast, PDE1C levels decreased in all conditions that inhibited proliferation. This mirrored the enzymatic activity of both PDE5 and PDE1C. Increasing cGMP intracellular levels by dbcGMP or sildenafil treatments did not block proliferation, while dbcAMP inhibited myometrial cell proliferation. Together, these results suggest that PDE5 regulation of cGMP intracellular levels is not involved in the control of SMC cycle progression, but may represent one of the markers of the contractile phenotype. 相似文献
40.
This article selectively reviews research concerning nicotine's effects on cognition, including the neurobiological mechanism for these effects, task and experimental features that may be important for elucidating these effects, and why these effects may have amplified motivational significance among smokers with cognitive deficit. Nicotine has effects on various cognitive processes, though most studies in humans have focused on the amelioration of cognitive deficits experienced during drug withdrawal. The direct cognitive-enhancing effect of nicotine remains a controversial topic. The relationship between attentional and non-attentional cognitive effects of nicotine is discussed in the context of cognitive self-medication. Further research should include theory-driven examination of cognitive effects of nicotine, and develop targeted smoking cessation programs based on an improved understanding of the role of cognitive self-medication in high-risk individuals. 相似文献