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61.
Background
Unravelling the path from genotype to phenotype, as it is influenced by an organism's environment, is one of the central goals in biology. Gene expression profiling by means of microarrays has become very prominent in this endeavour, although resources exist only for relatively few model systems. As genomics has matured into a comparative research program, expression profiling now also provides a powerful tool for non-traditional model systems to elucidate the molecular basis of complex traits. 相似文献62.
63.
Berezin MY Guo K Akers W Livingston J Solomon M Lee H Liang K Agee A Achilefu S 《Biochemistry》2011,50(13):2691-2700
We demonstrate that the structure of carbocyanine dyes, which are commonly used to label small peptides for molecular imaging and not the bound peptide, controls the rate of extravasation from blood vessels to tissue. By examining several near-infrared (NIR) carbocyanine fluorophores, we demonstrate a quantitative correlation between the binding of a dye to albumin, a model plasma protein, and the rate of extravasation of the probe into tissue. Binding of the dyes was measured by fluorescence quenching of the tryptophans in albumin and was found to be inversely proportional to the rate of extravasation. The rate of extravasation, determined by kurtosis from longitudinal imaging studies using rodent ear models, provided a basis for quantitative measurements. Structure-activity studies aimed at evaluating a representative library of NIR fluorescent cyanine probes showed that hydrophilic dyes with binding constants several orders of magnitude lower than their hydrophobic counterparts have much faster extravasation rate, establishing a foundation for rational probe design. The correlation provides a guideline for dye selection in optical imaging and a method to verify if a certain dye is optimal for a specific molecular imaging application. 相似文献
64.
Estrous behavior in response to ambient and long-day photoperiods was evaluated in ewes developed by 10 years of selection for ability to lamb in autumn. Following October lambing, 67 ewes were moved indoors and exposed to long-day (16L:8D) or ambient photoperiods from February 2 until July 6. Two vasectomized rams with marking harnesses were housed with each group. Estrous behavior was monitored twice weekly. Ewes from the selection line were unresponsive to long days, with no effects on estrous behavior, frequency of ovulation, or circulating prolactin. Adult ewes were anestrus for only 34±3 d, but 2- and 3-years-old ewes were anestrus for 72±7 and 57±10 d, respectively. Frequencies of ovulation based on circulating progesterone concentrations in March, May, and June were 97%, 95% and 52%, respectively, indicating that many ewes that did not exhibit estrus still ovulated. Prolactin concentrations increased from 10 ng/ml in February to 27 ng/ml in March and 173 ng/ml in June but were not affected by light treatment. Ten ewes that failed to exhibit estrus behavior for at most 24 d during the main study were then monitored for 74 additional long days. Nine of 10 ewes did not exhibit estrus for periods similar to 1 or 2 estrus cycles during this period, but eight ewes re-initiated cycles by the end of the study on September 18. Selection for ability to lamb in autumn thus resulted in ewes with an abbreviated seasonal anestrus and reduced sensitivity to long days. 相似文献
65.
66.
Letícia Muraro Wildner Maria Luiza Bazzo Susie Coutinho Liedke Christiane Louren?o Nogueira Gabriela Segat Simone Gon?alves Senna Aline Daiane Schlindwein Jaquelline Germano de Oliveira Darcita B Rovaris Claudio A Bonjardim Erna G Kroon Paulo CP Ferreira 《Memórias do Instituto Oswaldo Cruz》2014,109(3):356-361
The identification of mycobacteria is essential because tuberculosis (TB) and
mycobacteriosis are clinically indistinguishable and require different therapeutic
regimens. The traditional phenotypic method is time consuming and may last up to 60
days. Indeed, rapid, affordable, specific and easy-to-perform identification methods
are needed. We have previously described a polymerase chain reaction-based method
called a mycobacteria mobility shift assay (MMSA) that was designed for
Mycobacterium tuberculosis complex (MTC) and nontuberculous mycobacteria
(NTM) species identification. The aim of this study was to assess the MMSA for the
identification of MTC and NTM clinical isolates and to compare its performance with
that of the PRA-hsp65 method. A total of 204 clinical isolates (102
NTM and 102 MTC) were identified by the MMSA and PRA-hsp65. For
isolates for which these methods gave discordant results, definitive species
identification was obtained by sequencing fragments of the 16S rRNA and
hsp65 genes. Both methods correctly identified all MTC isolates. Among
the NTM isolates, the MMSA alone assigned 94 (92.2%) to a complex or species, whereas
the PRA-hsp65 method assigned 100% to a species. A 91.5% agreement
was observed for the 94 NTM isolates identified by both methods. The MMSA provided
correct identification for 96.8% of the NTM isolates compared with 94.7% for
PRA-hsp65. The MMSA is a suitable auxiliary method for routine
use for the rapid identification of mycobacteria. 相似文献
67.
Edwards WB Xu B Akers W Cheney PP Liang K Rogers BE Anderson CJ Achilefu S 《Bioconjugate chemistry》2008,19(1):192-200
The combination of different imaging modalities, each providing information according to its strengths, can be a powerful method for diagnosing diseases. We have synthesized a monomolecular multimodal imaging agent (MOMIA), LS172, containing a subtype-2 somatostatin receptor (SSTr2)-avid peptide (Y3-octreotate or Y3-TATE), a radiometal chelating group (DOTA) and a near-infrared (NIR) fluorescent dye (cypate). In addition to optical methods, radiolabeling LS172 with 64Cu and 177Lu provides a strategy for in vitro evaluation or in vivo multimodal imaging by positron emission tomography (PET) and single photon emission computed tomography (SPECT), respectively. Determination of the binding affinity of LS172, nat Cu- and nat Lu-LS172 in SSTr2-transfected A427 cells (A427-7) showed that they all displayed high binding affinity toward SSTr2 with K i values of 0.234 nM, 11.5 nM, and 2.15 nM respectively. In contrast to cypate-labeled Y3-TATE (cytate), fluorescence microscopy showed that LS172 and nat Cu-LS172 accumulate modestly in A427-7 cells by SSTr2-mediated endocytosis, in spite of their relatively high binding affinity. In vivo, the biodistribution of the SSTr2 receptor specific 64Cu- and 177Lu-LS172 in AR42J tumor-bearing rats exhibited low (90% ID/liver). Both optical and radionuclear biodistribution studies showed a similar in vivo distribution profile. Surprisingly, the strong binding of LS172 to SSTr2 did not translate into high SSTr2-mediated endocytosis in cells or uptake in tumor in vivo. Considering that LS172 is a putative antagonist, the poor accumulation of the labeled MOMIAs in SSTr2 positive tumor tissue supports the paradigm that agonists with their concomitant internalization favors appreciable target tissue accumulation of receptor-specific ligands. 相似文献
68.
Marcilio CP de Souto Ivan G Costa Daniel SA de Araujo Teresa B Ludermir Alexander Schliep 《BMC bioinformatics》2008,9(1):497
Background
The use of clustering methods for the discovery of cancer subtypes has drawn a great deal of attention in the scientific community. While bioinformaticians have proposed new clustering methods that take advantage of characteristics of the gene expression data, the medical community has a preference for using "classic" clustering methods. There have been no studies thus far performing a large-scale evaluation of different clustering methods in this context. 相似文献69.
Early experience is known to have a profound impact on brain and behavioral function later in life. Relatively few studies, however, have examined whether the effects of early experience remain detectable in the aging animal. Here, we examined the effects of neonatal novelty exposure, an early stimulation procedure, on late senescent rats' ability to win in social competition. During the first 3 weeks of life, half of each litter received daily 3-min exposures to a novel environment while the other half stayed in the home cage. At 24 months of age, pairs of rats competed against each other for exclusive access to chocolate rewards. We found that novelty-exposed rats won more rewards than home-staying rats, indicating that early experience exerts a life-long effect on this aspect of social dominance. Furthermore, novelty-exposed but not home-staying rats exhibited habituation of corticosterone release across repeated days of social competition testing, suggesting that early experience permanently enhances plasticity of the stress response system. Finally, we report a surprising finding that across individual rat families, greater effects of neonatal novelty exposure on stress response plasticity were found among families whose dams provided more reliable, instead of a greater total quantity of, maternal care. 相似文献
70.
Microsporidia, amitochondrial protists, possess a 70-kDa heat shock protein gene of mitochondrial evolutionary origin 总被引:13,自引:3,他引:10
Peyretaillade E; Broussolle V; Peyret P; Metenier G; Gouy M; Vivares CP 《Molecular biology and evolution》1998,15(6):683-689
An intronless gene encoding a protein of 592 amino acid residues with
similarity to 70-kDa heat shock proteins (HSP70s) has been cloned and
sequenced from the amitochondrial protist Encephalitozoon cuniculi (phylum
Microsporidia). Southern blot analyses show the presence of a single gene
copy located on chromosome XI. The encoded protein exhibits an N-terminal
hydrophobic leader sequence and two motifs shared by proteobacterial and
mitochondrially expressed HSP70 homologs. Phylogenetic analysis using
maximum likelihood and evolutionary distances place the E. cuniculi
sequence in the cluster of mitochondrially expressed HSP70s, with a higher
evolutionary rate than those of homologous sequences. Similar results were
obtained after cloning a fragment of the homologous gene in the closely
related species E. hellem. The presence of a nuclear targeting signal-like
sequence supports a role of the Encephalitozoon HSP70 as a molecular
chaperone of nuclear proteins. No evidence for cytosolic or endoplasmic
reticulum forms of HSP70 was obtained through PCR amplification. These data
suggest that Encephalitozoon species have evolved from an ancestor bearing
mitochondria, which is in disagreement with the postulated presymbiotic
origin of Microsporidia. The specific role and intracellular localization
of the mitochondrial HSP70-like protein remain to be elucidated.
相似文献