Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Functional differentiation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed2004

Differential functional expression of human myocardial G protein receptor kinases in left ventricular cardiac diseases.

The relationship between myocardial G protein receptor kinase (GRK) expression and beta-adrenoceptor signalling in human left heart diseases has not been fully elucidated yet. In this study, we characterized and compared the GRK2-7 expression in patients with left ventricular volume overload disorders and dilated cardiomyopathic hearts, and evaluated the relationship of this expression with alterations in myocardial beta-adrenoceptor signalling in volume overload, in order to test the notion that GRK functional expression is influenced in a disease-specific and selective fashion. We established that GRK2, GRK3, and GRK5 are well expressed, while GRK4, GRK6, and GRK7 are only scarcely detectable in the healthy human heart. Compared to control hearts (n=8), GRK2 mRNA expression was elevated by 71% (P<0.005) in the left ventricle, 110% (P<0.05) in the right ventricle, 130% (P<0.05) in the left atrium, and 1300% (P<0.005) in the right atrium (RA) of the dilated cardiomyopathy hearts (n=6). In the volume overload group (n=10), it was increased by approximately 40% (P<0.05) in the left ventricle, 38% in the right ventricle, 81% (P<0.05) in the left atrium, and 850% (P<0.005) in the right atrium. On the other hand, GRK5 was significantly elevated only in the left ventricle by 68% (P<0.05) in the dilated cardiomyopathy hearts and by 48% (P<0.01) in volume overload patients, while in contrast, GRK3 remained unchanged in dilated cardiomyopathy, but was slightly elevated by 36% (P=0.05) in the right ventricle of the volume overload patients. The alterations in GRK expression were accompanied with a decrease in myocardial beta(1)-adrenoceptor mRNA in all four chambers, and these trends in gene expression were paralleled with those of their immunodetectable protein levels. Furthermore, these changes were in association with a decrease in downstream receptor-stimulated, adenylyl cyclase-mediated functional expression and an increase in ventricular protein kinase A activity. The results point to differences in which myocardial GRKs are regulated in cardiac disease, whereby changes in GRK2 expression may be related to the global effects of the disease on myocardial adrenoceptor function and those in GRK5 may be localized to the ventricles, depending on the nature of the myocardial load.

Adenylyl Cyclase Inhibitors↗
PubMed2003

Differential function and expression of the viral inhibitor of caspase 8-induced apoptosis (vICA) and the viral mitochondria-localized inhibitor of apoptosis (vMIA) cell death suppressors conserved in primate and rodent cytomegaloviruses.

Human cytomegalovirus (CMV) genes UL36 and UL37 encode viral inhibitor of caspase-8-induced apoptosis (vICA) and viral mitochondria inhibitor of apoptosis (vMIA), respectively. Rhesus macaque CMV homologues, denoted Rh-vICA and Rh-vMIA, were identified and found to suppress apoptosis. One of these functions was conserved in MCMV, encoded by the M36 gene and denoted M-vICA. Conserved regions were compared to domains important to vICA- and vMIA-mediated cell death suppression. The conserved sequences of primate CMV vMIA homologues overlapped with the two known functional domains, providing further evidence supporting a crucial role of vMIA in cell death suppression. RNA blot analyses revealed that expression of murine and rhesus macaque CMV UL36 and UL37 homologues started early and continued through late times of infection. Murine CMV homologues were expressed with alpha (immediate early) kinetics, like human CMV UL36 and UL37, whereas rhesus macaque CMV homologues exhibited beta (delayed early) kinetics. Despite differences in organization and transcriptional regulation, this region appears to carry out a conserved role in cell death suppression. When viewed in light of sequence conservation, a functional vMIA homologue appears to be encoded by every primate CMV, whereas a functional vICA homologue appears to be encoded by all cytomegaloviruses for which sequence data are available.

Amino Acid Sequence↗
PubMed2005

Differential functional effects of two 5-HT4 receptor isoforms in adult cardiomyocytes.

Serotonin 5-HT4 receptors are present in human atrial myocytes and have been proposed to contribute to the generation of atrial fibrillation. However, 5-HT4 receptors have so far been only found in human and pig atria and are absent from the heart of small laboratory animals, such as rat, guinea pig, rabbit and frog, which limits the experimental settings for studying their functional properties. In this study, we developed an adenovirus expression system to examine the properties of two human 5-HT4 receptor splice variants, h5-HT4(b) and h5-HT4(d), expressed in adult cardiomyocytes devoid of native 5-HT4 receptors. When expressed in the HL-1 murine cell line of atrial origin, both receptors caused specific binding of the 5-HT4 selective antagonist GR113808 and activated adenylyl cyclase in the presence of serotonin (5-HT, 1 microM). When expressed in freshly isolated adult rat ventricular cardiomyocytes, a stimulation of the L-type Ca2+ current (ICa,L) by 5-HT (100 nM) was revealed. Both effects were blocked by GR113808. In HL-1 cells, the h5-HT4(d) receptor was found to be more efficiently coupled to adenylyl cyclase than the h5-HT4(b). Pertussis toxin treatment (250 ng/ml for 5 h) potentiated the stimulatory effect of 5-HT on ICa,L in rat myocytes expressing the h5-HT4(b) but not the h5-HT4(d) receptor, indicating a likely coupling of the (b) isoform to both Gs and Gi/o proteins. Adenoviral expression of h5-HT4 receptor isoforms in adult cardiac myocytes provides a valuable means for the exploration of the receptor signaling cascades in normal and pathological situations.

Adenoviridae↗
PubMed1999

Differential function of the two nucleotide binding domains on cystic fibrosis transmembrane conductance regulator.

The genetic disease cystic fibrosis is caused by defects in the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR). CFTR belongs to the family of ABC transporters. In contrast to most other members of this family which transport substrates actively across a membrane, the main function of CFTR is to regulate passive flux of substrates across the plasma membrane. Chloride channel activity of CFTR is dependent on protein phosphorylation and presence of nucleoside triphosphates. From electrophysiological studies of CFTR detailed models of its regulation by phosphorylation and nucleotide interaction have evolved. These investigations provide ample evidence that ATP hydrolysis is crucial for CFTR gating. It becomes apparent that the two nucleotide binding domains on CFTR not only diverge strongly in sequence, but also in function. Based on previous models and taking into account new data from pre-steady-state experiments, a refined model for the action of nucleotides at two nucleotide binding domains was recently proposed.

ATP-Binding Cassette Transporters↗
PubMed1993

Functional differentiation in progesterone secretion by granulosa versus cumulus cells in the human preovulatory follicle and the effect of different induction of ovulation protocols.

OBJECTIVE: To investigate P secretion by granulosa cells (GCs) versus cumulus cells derived from human preovulatory follicles. DESIGN: Cells were recovered by aspiration of preovulatory follicles in 44 women participating in an IVF program. Induction of ovulation was performed using clomiphene citrate, hMG and hCG (group I), hMG/hCG (group II), buserelin acetate/hMG/hCG (group III), or Decapeptyl/hMG/hCG (group IV). SETTING: Laboratories of the IVF Unit at the Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel. MAIN OUTCOME MEASURES: Secretion of P was examined after cultures for 96 hours under nonstimulated and hCG stimulated conditions. RESULTS: Progesterone secretion by GCs derived from all four groups was found to be higher compared with the respective cumulus cells. However, although the ratios of P secretion by GCs versus cumulus cells in groups I, II, and III were very similar, a significantly lower value was observed in group IV. The response of GCs to hCG in terms of P secretion was higher with at least one dose of hCG in groups I and IV compared with groups II and III. The response of cumulus cells to hCG was absent regardless of the treatment protocol used in vivo. CONCLUSION: Our results demonstrate that in the human preovulatory follicle, GCs and cumulus cells differ in their capacity to secrete P as well as in their response to hCG. They further suggest that the mode of induction of ovulation affects the relative capacity of GCs and cumulus cells to secrete P and their ability to respond to hCG.

Adult↗
PubMed1997

Picolinic acid and indole-2-carboxylic acid: two types of glycinergic compounds modulate motor function differentially.

1. A putative agonist for the strychnine-sensitive glycine receptor picolinic acid was tested for its anticonvulsant activities in mice and muscle-relaxant activities in rats and compared with indole-2-carboxylic acid (I2CA), an antagonist for the strychnine-insensitive glycine receptor. Their effects on segmental reflexes in the cat spinal cord were examined to elucidate their sites of action. 2. Picolinic acid (200 and 400 mg/kg IP) delayed the onsets of strychnine- but not pentylenetetrazole-induced seizures. It delayed the onsets of bicuculline-induced seizures only at the higher dose. I2CA (200 and 400 mg/kg IP) delayed the onsets of these 3 kinds of seizures. Both compounds reduced muscle tone in rat decerebrate rigidity at a dose of 100 mg/kg IV. 3. Picolinate methylester, a picolinate derivative with higher lipophilicity, depressed spinal reflexes in both intact and spinalized cats at cumulative doses of 25 to 200 mg/kg IV. I2CA (50 mg/kg IV) inhibited spinal reflexes only in intact preparations. 4. These results suggest that the anticonvulsant and muscle-relaxant activities of picolinic acid (PA) are due to inhibition of spinal neurons, but that I2CA selectively affects supraspinal structures.

Animals↗
PubMed2001

Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock.

The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes. Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness. Clock gene RNA rhythms were blunted in the suprachiasmatic nucleus of mPer2 mutant mice, but not of mPER1-deficient mice. Peak mPER and mCRY1 protein levels were reduced in both lines. Behavioral rhythms of mPer1/mPer3 and mPer2/mPer3 double-mutant mice resembled rhythms of mice with disruption of mPer1 or mPer2 alone, respectively, confirming the placement of mPer3 outside the core circadian clockwork. In contrast, mPer1/mPer2 double-mutant mice were immediately arrhythmic. Thus, mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes.

Animals↗
PubMed2003

Functional differentiation of multiple climbing fiber inputs during synapse elimination in the developing cerebellum.

We studied how physiological properties of cerebellar climbing fiber (CF) to Purkinje cell (PC) synapses change during developmental transition from multiple to mono CF innervation onto each PC. From P3 to P6, differences in the strengths of multiple CFs became larger. Around P10, each PC was either monoinnervated by one strong CF (CF-mono) or multiply innervated by one strong CF (CF-multi-S) plus a few weaker CFs (CF-multi-W). We show that simultaneous release of multiple vesicles per site occurs normally from CF-multi-S, CF-mono, and mature CFs, but less frequently from CF-multi-W and neonatal CFs. We also present evidence suggesting that weaker CFs with lower probability of multivesicular release would be withdrawn preferentially. The results suggest that differentiation into strong and weak CFs with high and low probabilities of multivesicular release precedes developmental CF synapse elimination.

Afferent Pathways↗
PubMedDate not supplied

Anatomical and functional differentiation of glutamatergic synaptic innervation in the neocortex.

Pyramidal neurons are the principal neurons of the neocortex and their excitatory impact on other pyramidal neurons and interneurons is central to neocortical dynamics. A fundamental principal that has emerged which governs pyramidal neuron excitation of other neurons in the local circuitry of neocortical columns is differential anatomical and physiological properties of the synaptic innervation via the same axon depending on the type of neuron targeted. In this study we derive anatomical principles for divergent innervation of pyramidal neurons of the same type within the local microcircuit. We also review data providing circumstantial and direct evidence for differential synaptic transmission via the same axon from neocortical pyramidal neurons and derive some principles for differential synaptic innervation of pyramidal neurons of the same type, of pyramidal neurons and interneurons and of different types of interneurons. We conclude that differential anatomical and physiological differentiation is a fundamental property of glutamatergic axons of pyramidal neurons in the neocortex.

Animals↗
PubMed2000

New non-woven polyurethane-based biomaterials for the cultivation of hepatocytes: expression of differentiated functions.

A new non-woven polyetherurethane support suitable to host cultured hepatocytes has been developed. Prior to its use in bioreactors and artificial liver devices, the biocompatibility of this new material was investigated. The experiments have shown that the survival and functionality of hepatocytes entrapped in the non-woven polymer were longer than that of monolayer cultured hepatocytes, under serum-free culture conditions. Hepatic specific metabolic functions, namely, synthesis of urea and synthesis and secretion of plasma proteins, were well maintained by hepatocytes entrapped in non-woven polyetherurethane sheets. Cells also retained the expression of biotransformation activities of 7-ethoxycoumarin-O-deethylase as well as CYP2A1, CYP2B1 and CYP3A1. The results presented in this paper point to non-woven polyetherurethane sheets as a suitable biocompatible support for functional, three-dimensional hepatocyte cultures.

Journal Article↗
PubMed2003

Adult age differences in multiple cognitive functions: differentiation, dedifferentiation, or process-specific change?

Adult age differences in covariance structures of latent variables of vocabulary, list recall, speed, working memory, and text recall, were analyzed to test hypotheses of structural changes with age. There were baseline data from 613 men and women aged 30-97, data from a second wave of testing from 322 people, and complete longitudinal data from 289 people. There were age differences in the size but not configuration of factor loadings cross-sectionally but not longitudinally. There were no changes in factor standard deviations or covariances. Findings did not support models of dedifferentiation with age.

Adult↗
PubMed1976

Functional differentiation within the neostriatum of the rat using electrical (blocking) stimulation during discrimination learning.

Sixteen rats, eight with bipolar electrodes implanted bilaterally in the anterodorsal head of the caudate-putamen and eight with similar electrodes in the posteroventral caudate-putamen, learned a spatial and a form discrimination task and their reversals while receiving "continuous" stimulation. Rats receiving stimulation to the anterodorsal caudate-putamen were imparied on spatial reversal learning compared with the posteroventral group. On form discrimination reversal the posteroventral group were impaired compared with the anterodorsal group. This dissociation is related to the particular cortical neostriatal projection system for the region stimulated and demonstrates a behavioral differentiation in rat neostriatum comparable with that observed in the monkey.

Animals↗