Measurement of heart rate and Q-T interval in the conscious mouse

1998 ◽  
Vol 274 (3) ◽  
pp. H747-H751 ◽  
Author(s):  
Gary F. Mitchell ◽  
Andreas Jeron ◽  
Gideon Koren
Keyword(s):  
Specific Gene ◽  
Telemetry System ◽  
Square Root ◽  
Gene Products ◽  
Minimal Effect ◽  
Transgenic Mouse Models ◽  
Cardiac Ion Channels ◽  
Ketamine Anesthesia ◽  
Conscious Animals ◽  
Over Time

Transgenic mouse models provided a powerful tool to evaluate the physiological significance of altered quantities or characteristics of specific gene products, such as cardiac ion channels. We have developed a system to record and analyze changes in the electrocardiogram in the mouse using an implantable telemetry system. The R-R and Q-T intervals were measured on individual beats and on signal-averaged complexes derived from 1, 2, or 4 s of contiguous data each hour during a 24-h period in three male and three female FVB mice. Duration of averaging had minimal effect on the measured Q-T. The Q-T interval was shown to be related to the square root of the R-R interval, and an appropriate formula for a rate-corrected Q-T interval (Q-Tc) was derived. Ketamine anesthesia was shown to markedly increase duration and variability in R-R, Q-T, and Q-Tc intervals. In conscious animals, variability in Q-T was low across animals and over time, suggesting that this should be a sensitive model for detection of changes in the Q-T interval in transgenic mice with ion channel defects.

scholarly journals Transcription of Candidate Virulence Genes ofHaemophilus ducreyi during Infection of Human Volunteers

2001 ◽  
Vol 69 (3) ◽  
pp. 1483-1487 ◽  
Author(s):  
Robert E. Throm ◽  
Stanley M. Spinola
Keyword(s):  
Experimental Infection ◽  
Virulence Genes ◽  
Human Model ◽  
Specific Gene ◽  
Gene Products ◽  
Virulence Determinants ◽  
Reverse Transcription Pcr ◽  
Human Volunteers

ABSTRACT Haemophilus ducreyi expresses several putative virulence factors in vitro. Isogenic mutant-to-parent comparisons have been performed in a human model of experimental infection to examine whether specific gene products are involved in pathogenesis. Several mutants (momp, ftpA, losB, lst, cdtC, and hhdB) were as virulent as the parent in the human model, suggesting that their gene products did not play a major role in pustule formation. However, we could not exclude the possibility that the gene of interest was not expressed during the initial stages of infection. Biopsies of pustules obtained from volunteers infected with H. ducreyiwere subjected to reverse transcription-PCR. Transcripts corresponding to momp, ftpA, losB, lst, cdtB, and hhdA were expressed in vivo. In addition, transcripts for other putative virulence determinants such as ompA2, tdhA, lspA1, andlspA2 were detected in the biopsies. These results indicate that although several candidate virulence determinants are expressed during experimental infection, they do not have a major role in the initial stages of pathogenesis.

Dimerization through the helix-loop-helix motif enhances phosphorylation of the transcription activation domains of myogenin

1994 ◽  
Vol 14 (9) ◽  
pp. 6232-6243
Author(s):  
J Zhou ◽  
E N Olson
Keyword(s):  
Transcriptional Activity ◽  
Transcription Activation ◽  
Bhlh Protein ◽  
Specific Gene ◽  
Phosphorylation Sites ◽  
Gene Products ◽  
Activation Domains ◽  
Helix Loop Helix ◽  
Carboxyl Terminal ◽  
Bhlh Proteins

The muscle-specific basic helix-loop-helix (bHLH) protein myogenin activates muscle transcription by binding to target sequences in muscle-specific promoters and enhancers as a heterodimer with ubiquitous bHLH proteins, such as the E2A gene products E12 and E47. We show that dimerization with E2A products potentiates phosphorylation of myogenin at sites within its amino- and carboxyl-terminal transcription activation domains. Phosphorylation of myogenin at these sites was mediated by the bHLH region of E2A products and was dependent on dimerization but not on DNA binding. Mutations of the dimerization-dependent phosphorylation sites resulted in enhanced transcriptional activity of myogenin, suggesting that their phosphorylation diminishes myogenin's transcriptional activity. The ability of E2A products to potentiate myogenin phosphorylation suggests that dimerization induces a conformational change in myogenin that unmasks otherwise cryptic phosphorylation sites or that E2A proteins recruit a kinase for which myogenin is a substrate. That phosphorylation of these dimerization-dependent sites diminished myogenin's transcriptional activity suggests that these sites are targets for a kinase that interferes with muscle-specific gene expression.

scholarly journals Enabling out-of-clinic human immunity studies via single-cell profiling of capillary blood

2020 ◽  
Author(s):  
Tatyana Dobreva ◽  
David Brown ◽  
Jong Hwee Park ◽  
Matt Thomson
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Environmental Factors ◽  
Single Cell ◽  
Immune Cell ◽  
Cell Types ◽  
Capillary Blood ◽  
Specific Gene ◽  
Human Immune ◽  
Over Time

AbstractAn individual’s immune system is driven by both genetic and environmental factors that vary over time. To better understand the temporal and inter-individual variability of gene expression within distinct immune cell types, we developed a platform that leverages multiplexed single-cell sequencing and out-of-clinic capillary blood extraction to enable simplified, cost-effective profiling of the human immune system across people and time at single-cell resolution. Using the platform, we detect widespread differences in cell type-specific gene expression between subjects that are stable over multiple days.SummaryIncreasing evidence implicates the immune system in an overwhelming number of diseases, and distinct cell types play specific roles in their pathogenesis.1,2 Studies of peripheral blood have uncovered a wealth of associations between gene expression, environmental factors, disease risk, and therapeutic efficacy.4 For example, in rheumatoid arthritis, multiple mechanistic paths have been found that lead to disease, and gene expression of specific immune cell types can be used as a predictor of therapeutic non-response.12 Furthermore, vaccines, drugs, and chemotherapy have been shown to yield different efficacy based on time of administration, and such findings have been linked to the time-dependence of gene expression in downstream pathways.21,22,23 However, human immune studies of gene expression between individuals and across time remain limited to a few cell types or time points per subject, constraining our understanding of how networks of heterogeneous cells making up each individual’s immune system respond to adverse events and change over time.

scholarly journals Hypothesis: protein and RNA attributes are continuously optimized over time

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sidney B. Cambridge
Keyword(s):  
Protein Structure ◽  
Gene Function ◽  
Protein Abundance ◽  
Gene Products ◽  
Gene Conservation ◽  
New Genes ◽  
Temporal Path ◽  
Gene Age ◽  
Over Time

Abstract Background Little is known why proteins and RNAs exhibit half-lives varying over several magnitudes. Despite many efforts, a conclusive link between half-lives and gene function could not be established suggesting that other determinants may influence these molecular attributes. Results Here, I find that with increasing gene age there is a gradual and significant increase of protein and RNA half-lives, protein structure, and other molecular attributes that tend to affect protein abundance. These observations are accommodated in a hypothesis which posits that new genes at ‘birth’ are not optimized and thus their products exhibit low half-lives and less structure but continuous mutagenesis eventually improves these attributes. Thus, the protein and RNA products of the oldest genes obtained their high degrees of stability and structure only after billions of years while the products of younger genes had less time to be optimized and are therefore less stable and structured. Because more stable proteins with lower turnover require less transcription to maintain the same level of abundance, reduced transcription-associated mutagenesis (TAM) would fixate the changes by increasing gene conservation. Conclusions Consequently, the currently observed diversity of molecular attributes is a snapshot of gene products being at different stages along their temporal path of optimization.

Localization and Visualization of Specific Gene Products in Fungal Plant Pathogens

2000 ◽  
Vol 6 (S2) ◽  
pp. 680-681 ◽  
Author(s):  
T. M. Bourett ◽  
K. J. Czymmek ◽  
T. M. Dezwaan ◽  
J. A. Sweigard ◽  
R. J. Howard
Keyword(s):  
Fungal Pathogens ◽  
Plant Pathogens ◽  
Protein Localization ◽  
Infected Plant ◽  
Cell Interaction ◽  
Specific Gene ◽  
Gene Products ◽  
Tem Analysis ◽  
Fungal Plant Pathogens ◽  
Plant Pathogenesis

Specific gene products of both pathogens and hosts have been implicated as decisive elements during plant pathogenesis. While expression of some of these genes is constitutive, that of others is likely ephemeral and activated only during a particular stage of the interaction. Because the relative timing of expression may be critical, transcription and translation have often been addressed by extracting mRNA and proteins from infected plant tissue. This approach, however, cannot readily detect proteins of low abundance in bulk samples nor offer much useful information on cell-cell interaction. Only a cytological analysis that employs microscopy can resolve the temporal and spatial details of gene expression. Typically, such protein localization studies have required specific antibodies, but these large probe molecules do not diffuse into living or conventionally fixed cells of either fungal pathogens or plant hosts. For TEM analysis, these permeability-imposed limitations have been reduced by thin sectioning to render accessible antibody binding sites.

scholarly journals Dexamethasone-dependent inhibition of differentiation of C2 myoblasts bearing steroid-inducible N-ras oncogenes.

1988 ◽  
Vol 106 (6) ◽  
pp. 2127-2137 ◽  
Author(s):  
L A Gossett ◽  
W Zhang ◽  
E N Olson
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Specific Gene ◽  
Dependent Manner ◽  
Gene Products ◽  
Ras Proteins ◽  
Inhibitory Effects ◽  
Specific Gene Expression ◽  
Ras Oncogenes ◽  
Inhibition Of Differentiation

ras proteins are localized to the plasma membrane where they are postulated to interact with growth factor receptors and other proximal elements in intracellular cascades triggered by growth factors. The molecular events associated with terminal differentiation of certain skeletal myoblasts are inhibited by specific polypeptide growth factors and by constitutive expression of transforming ras oncogenes. To determine whether the inhibitory effects of ras on myogenic differentiation were reversible and to investigate whether muscle-specific genes remained susceptible to ras-dependent repression in terminally differentiated myotubes, the murine myoblast cell line, C2, was transfected with a plasmid containing a mutationally activated human N-ras oncogene under transcriptional control of the steroid-sensitive promoter of the mouse mammary tumor virus long terminal repeat. Addition of dexamethasone to myoblasts bearing steroid-inducible ras oncogenes prevented myotube formation and induction of muscle creatine kinase and acetylcholine receptors. Inhibition of differentiation by dexamethasone occurred in a dose-dependent manner and was a titratable function of ras expression. In the presence of dexamethasone, myoblasts bearing steroid-inducible ras genes retained their dependence on exogenous growth factors to divide and exhibited contact inhibition of growth at confluent densities, indicating that the inhibitory effects of ras on differentiation were independent of cell proliferation. Removal of dexamethasone from N-ras-transfected myoblasts led to fusion and induction of muscle-specific gene products in a manner indistinguishable from control C2 cells. Examination of the effects of culture media conditioned by ras-transfected myoblasts on differentiation of normal C2 cells yielded no evidence for inhibition of differentiation via an autocrine mechanism. In contrast to the ability of N-ras to prevent up-regulation of muscle-specific gene products in myoblasts, induction of N-ras in terminally differentiated myotubes failed to extinguish muscle-specific gene expression. Together, these results suggest that oncogenic ras proteins reversibly activate an intracellular cascade that prevents establishment of the differentiated phenotype. The inability of ras to extinguish muscle-specific gene expression in terminally differentiated myotubes also suggests that ras may interfere with an early step in the pathway of myoblasts toward the differentiated state.

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