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At least 109 records · Page 6Linked to original sources
PubMed2001

Interplay of pituitary adenylate cyclase-activating polypeptide with a silencer element to regulate the upstream promoter of the human gonadotropin-releasing hormone receptor gene.

Multiple transcription start sites were identified in the human gonadotropin releasing hormone receptor (hGnRHR) gene. Recently, an upstream promoter residing at -1727/-1674, in vicinity of a CAP site at -1673, was characterized. In this report, we elucidated the underlying mechanisms for the regulation of this promoter. Functionally, this promoter was constitutively suppressed by a silencer element (-1673/-1351) situated immediately downstream to it. On the other hand, pituitary adenylate cyclase-activating polypeptide (PACAP), via the cAMP pathway, was found to be the extracellular cue to control the upstream promoter. Following PACAP-27, PACAP-38 (30 nM) and forskolin (25 microM) treatment, there were significant increases in the reporter gene activities. By deletion analysis, the region residing at -1727 to -1577, containing the distal promoter and 97 bp of the silencer was subsequently found to be responsible for PACAP/cAMP induction. To localize the PACAP-dependent cis-acting element(s) within the silencer, block replacement scanning mutation was performed and a hGnRHR gene PACAP-responsive element (GPRE) was identified at -1676/-1648. The actions of PACAPs and forskolin on the GPRE were further evidenced by gel mobility shift assays. There was an increase in protein binding onto this element only after peptide treatment. As GnRH receptor number on gonadotrope cell surface is a key factor in regulating gonadotropin release, the present study provides an insight into the interplay between PACAP and GnRH receptors on pituitary gonadotropes to control human reproductive functions.

Base Sequence↗
PubMed2001

Interplay of biomechanical and neuromuscular constraints on pattern stability and attentional demands in a bimanual coordination task in human subjects.

Recent debate has focused upon the issue of whether general principles and laws of movement coordination may be derived without reference to anatomical, mechanical and physiological mechanisms. It has been proposed that self-generated movement involves the interaction of biomechanical and neuromuscular constraints. Biomechanical constraints are usually considered of as arising from the pendular dimensions of the limb or limb segments whereas neuromuscular constraints are commonly associated with nervous and metabolic control processes. The present study aims to investigate the interplay between these two different constraints on bimanual pattern stability and attentional demands. Five subjects were asked to execute an anti-phase coordination pattern (180 degrees of relative phase), while gradually increasing the frequency of oscillation and changing the rotational inertia of the joysticks. Frequency manipulation was expected to affect the neuromuscular constraints. Inertial manipulation was expected to affect biomechanical constraints. Attentional demands, reflecting the central cost associated with the maintenance of the coordination pattern was assessed using a dual-task paradigm. The results showed that: (1) increasing the oscillation frequency altered both coordination dynamics and attentional demands associated with the maintenance of bimanual coordination patterns; (2) manipulation of rotational inertia of the joysticks also altered pattern stability (standard deviation of relative phase) and coordination dynamics (i.e. the number of phase transition and the before transition), but these alterations were not paralleled by a change in attentional demands.

Adrenergic Agonists↗
PubMed2000

Functional interplay between gelatinases and hyperalgesia in endotoxin-induced localized inflammatory pain.

The role of ECM-degrading proteinases in normal developmental processes and in pathological conditions is extensively studied. However, few reports describe the role ECM-degrading proteinases play in modulating hyperalgesia. The goal of this study is to describe the regulation of gelatinases during endotoxin mediated local inflammation, induced by intra plantar endotoxin (ET; 1.25 microg/50 microl) injection in Balb/c mice, and to correlate that with hyperalgesia. ET injections induced hyperalgesia, as determined by hot plate and paw pressure tests, which peaked by 24 h and recovered by 48 h post-injection. Contralateral paw of ET injected mice and saline injected paws in control mice elicited no hyperalgesia. Zymography showed that ET and saline injected paws elicited increased gelatinase activity by 9 h after injection. However, only the former maintained high levels of expression of a 90 kD gelatinase up to at least 96 h post ET injection, while in the latter gelatinase expression was down regulated by 24 h. Interestingly, the 90-kD gelatinase was upregulated in the contralateral paw of the ET-injected mice beyond 48 h post injection. Saline injection in that paw, during a time when gelatinases are upregulated, induced hyperalgesia. Intraperitoneal injection of either ZnCl(2) (100 microM), thymulin (5 microg/100 microl), or morphine (2 mg/kg/100 microl) reversed the ET-induced hyperalgesia and suppressed gelatinase activity. Furthermore, intraperitoneal injection of MPI, an ECM-degrading proteinase inhibitor, reversed ET induced hyperalgesia. Taken together, the above suggests that a functional interplay exists between gelatinase upregulation triggered by ET injections and hyperalgesia. The exact mechanism underlying such correlation remains to be determined.

Animals↗
PubMed1997

The dynamic interplay of malignant and benign T cells in cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma is a malignancy of functional, tissue-specific T cells. Many characteristics of the disease can be explained by virtue of the ability of the malignant cell population to actively participate in the host's immunologic network. Various aspects of this dynamic interplay between malignant and benign T cells are discussed, including impact on diagnosis, staging, and therapy.

Diagnosis, Differential↗
PubMed2003

The interplay between education and research about patient-provider communication.

Attention to providers' communication skills is likely to increase, given the confluence of forces that have highlighted the importance of communication in healthcare. In the United States, interpersonal and communication skills have been explicitly identified as a priority throughout the continuum of medical education and practice. Ideally, theory and research inform teaching and assessment efforts by suggesting how communication behavior affects outcomes and by providing a conceptual framework for learning skills. This article illustrates the interplay between education and research by discussing examples of useful concepts (models of communication, issues of perceived control, and patterns of non-verbal communication) and understudied topics (physician verbalizations during patients' initial narratives, the mundane aspects of communication in healthcare, conceptual and operational definitions of empathy, and the effect of patient narratives on both patients and providers). Given the breadth and depth of experience, from screening and prevention to treatment and support, the context of cancer offers a promising laboratory for enhancing both education and research about provider-patient communication.

Clinical Competence↗
PubMed2002

Regulation of enzymatic lipid peroxidation: the interplay of peroxidizing and peroxide reducing enzymes.

For a long time lipid peroxidation has only been considered a deleterious process leading to disruption of biomembranes and thus, to cellular dysfunction. However, when restricted to a certain cellular compartment and tightly regulated, lipid peroxidation may have beneficial effects. Early on during evolution of living organisms special lipid peroxidizing enzymes, called lipoxygenases, appeared and they have been conserved during phylogenesis of plants and animals. In fact, a diverse family of lipoxygenase isoforms has evolved starting from a putative ancient precursor. As with other enzymes, lipoxygenases are regulated on various levels of gene expression and there are endogenous antagonists controlling their cellular activity. Among the currently known mammalian lipoxygenase isoforms only 12/15-lipoxygenases are capable of directly oxygenating ester lipids even when they are bound to membranes and lipoproteins. Thus, these enzymes represent the pro-oxidative part in the cellular metabolism of complex hydroperoxy ester lipids. Its metabolic counterplayer, representing the antioxidative part, appears to be the phospholipid hydroperoxide glutathione peroxidase. This enzyme is unique among glutathione peroxidases because of its capability of reducing ester lipid hydroperoxides. Thus, 12/15-lipoxygenase and phospholipid hydroperoxide glutathione peroxidase constitute a pair of antagonizing enzymes in the metabolism of hydroperoxy ester lipids, and a balanced regulation of the two proteins appears to be of major cell physiological importance. This review is aimed at summarizing the recent developments in the enzymology and molecular biology of 12/15-lipoxygenase and phospholipid hydroperoxide glutathione peroxidase, with emphasis on cytokine-dependent regulation and their regulatory interplay.

Animals↗
PubMed1998

Triple quantum MQMAS spectroscopy of 59Co(I = 7/2) in Na3Co(NO2)6 and trans-Co[(en2)(NO2)2]NO3 interplay between the quadrupole coupling and anisotropic shielding tensors.

The purpose of this paper is to investigate the interplay between the chemical shielding anisotropy and quadrupole interaction in MQMAS spectra. 59Co in the compounds Na3Co(NO2)6 and trans-Co[(en2)(NO2)2]NO3 provides model systems for such an investigation. Furthermore, only few results have been reported on the application of the MQMAS method to a spin I = 7/2. The possibilities of the MQMAS spectroscopy for determining the relative orientation of the two tensors and its advantage over previous techniques are discussed. Reported experimental spectra at different spinning speeds of Na3Co(NO2)6 are accurately reproduced by our theoretical simulations. The calculations are based on a recent approach, summarized in the present paper, which allows one to perform efficient simulations of MQMAS spectra including all interactions and their time-dependence throughout the experiment. This is necessary for calculating accurate MQMAS spectra including the spinning sideband pattern. In the case of trans-Co[(en2)(NO2)2]NO3 where the quadrupolar interaction and chemical shielding are stronger and their axes are non-coincident, the MQMAS spectrum is strongly distorted due to the unsufficient spinning speed and RF power. In this case, MAS at different spinning speeds is shown to provide valuable information.

Anisotropy↗
PubMed1997

Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways.

Cadherins play important roles in cell-cell adhesion during tissue differentiation. Cadherins are linked to the actin cytoskeleton by catenins (beta-catenin/armadillo, plakoglobin, and alpha-catenin). Recent results show that beta-catenin also binds to another cytoskeletal complex containing the adenomatous polyposis coli protein and microtubules, and interacts with several signaling pathways that include tyrosine kinases and phosphatases and Wnt/Wingless. Interplay between these cytoskeletal complexes and signaling pathways may regulate morphogenesis.

Animals↗
PubMed2003

Membrane fusion: a structural perspective on the interplay of lipids and proteins.

The fusion of biological membranes is governed by the carefully orchestrated interplay of membrane proteins and lipids. Recently determined structures of fusion proteins, individual domains of fusion proteins and their complexes with regulatory proteins and membrane lipids have yielded much suggestive insight into how viral and intracellular membrane fusion might proceed. These structures may be combined with new knowledge on the fusion of pure lipid bilayer membranes in an attempt to begin to piece together the complex puzzle of how biological membrane fusion machines operate on membranes.

Lipids↗
PubMed1997

Spermatogenesis in the vitamin A-deficient rat: possible interplay between retinoic acid receptors, androgen receptor and inhibin alpha-subunit.

In order to understand the mechanisms of retinol action on the testis, testicular retinoic acid receptor alpha, beta(RAR alpha and beta), androgen receptor (AR) and inhibin alpha-subunit were studied in normal, vitamin A-deficient (VAD) and vitamin A-supplemented rats by immunohistochemistry and immunoblotting. Compared to the normal testis, expression of 110 K AR was up-regulated by vitamin A withdrawal, whereas 51 K RAR alpha remained unchanged. An additional 55 K RAR alpha signal was observed. Readministration of retinol caused a marked decrease of AR in the VAD testis. By 24 h, AR declined to below the normal level. Although the 51 K RAR alpha signal remained unchanged, the 55 K band was slightly up-regulated at 6 h after retinol administration. A 51 K RAR beta protein was seen in the VAD but in not the normal testis. The intensity of the 51 K RAR beta band remained constant before and after the administration of retinol, but it had a slight up-shift at 6 h after retinol injection, suggesting post-translational modification of the receptor. The inhibin alpha-subunit of 18 K protein was undetectable in the VAD testis and increased to above normal level at 24 h after retinol administration. Immunohistochemically, nuclear AR immunostaining was more intense in the VAD testis than in the normal testis. The intensity of immunostaining declined in all AR-positive cells after the injection of retinol, but the decrease was more evident in Sertoli than in other cells. At 24 h after retinol the immunostaining was undetectable in most Sertoli cells. The regulation of the inhibin alpha-subunit by retinol in the cytoplasm of Sertoli cells detected by immunohistochemistry was correlated to the results in immunoblotting. These results suggest a possible interplay between retinoids, androgen and inhibin signalling systems in Sertoli cells in the regulation of spermatogenesis during retinol action.

Animals↗
PubMed2002

Interplay of TBP inhibitors in global transcriptional control.

The TATA binding protein (TBP) is required for the expression of nearly all genes and is highly regulated both positively and negatively. Here, we use DNA microarrays to explore the genome-wide interplay of several TBP-interacting inhibitors in the yeast Saccharomyces cerevisiae. Our findings suggest the following: The NC2 inhibitor turns down, but not off, highly active genes. Autoinhibition of TBP through dimerization contributes to transcriptional repression, even at repressive subtelomeric regions. The TAND domain of TAF1 plays a primary inhibitory role at very few genes, but its function becomes widespread when other TBP interactions are compromised. These findings reveal that transcriptional output is limited in part by a collaboration of different combinations of TBP inhibitory mechanisms.

Binding Sites↗
PubMed2003

Dynamic interplay of the SUMO and ERK pathways in regulating Elk-1 transcriptional activity.

The ETS domain transcription factor Elk-1 is a direct target of the MAP kinase pathways. Phosphorylation of the Elk-1 transcriptional activation domain by MAP kinases triggers its activation. However, Elk-1 also contains two domains with repressive activities. One of these, the R motif, appears to function by suppressing the activity of the activation domain. Here, we demonstrate that SUMO modification of the R motif is required for this repressive activity. A dynamic interplay exists between the activating ERK MAP kinase pathway and the repressive SUMO pathway. ERK pathway activation leads to both phosphorylation of Elk-1 and loss of SUMO conjugation and, hence, to the loss of the repressive activity of the R motif. Thus, the reciprocal regulation of the activation and repressive activities are coupled by MAP kinase modification of Elk-1.

Animals↗
PubMed1999

Interplay of global regulators and cell physiology in the general stress response of Escherichia coli.

Under various stress conditions, two sigma subunits of RNA polymerase, sigmaS and sigma70, coexist in Escherichia coli cells. In contrast to sigma70, sigmaS is subject to intricate regulation and coordinates an emergency reaction to stress as well as long term stress adaptation. In vivo, the two sigma factors clearly control different genes. Yet, they are structurally and functionally very similar and basically recognize the same promoter sequences. Recent data suggest that sigma factor specificity at stress-activated promoters is affected by the interplay of the two RNA polymeraseholoenzymes with additional regulatory factors, such as H-NS, Lrp, CRP, IHF or Fis, that differentially affect transcription initiation by sigmaS or sigma70 in a promoter-specific manner.

Adaptation, Biological↗
PubMed2001

Interplay in lipoplexes between type of pDNA promoter and lipid composition determines transfection efficiency of human growth hormone in NIH3T3 cells in culture.

This study was aimed to investigate if and to what extent there is an interplay between lipoplex physicochemical properties and plasmid promoter type affecting transfection efficiency in vitro. To reduce the number of variables only one cell type (NIH3T3 cells), one gene (human growth hormone), one cationic lipid (DOTAP) in a plasmid >85% in supercoiled form, and the same medium conditions were used. The variables of the physicochemical properties included presence and type of helper lipid (DOPE, DOPC, or cholesterol, all in 1:1 mole ratio with DOTAP), size and lamellarity of the liposomes used for lipoplex preparation (large unilamellar vesicles, LUV, versus multilamellar vesicles, MLV), and DNA(-)/cationic lipid(+) charge ratio, all containing the same human growth hormone but differing in their promoter enhancer region. Two of the promoters were of viral origin: (a) SV40 promoter (simian virus early promoter) and (b) CMV promoter (cytomegalovirus early promoter); two were of mammalian cell origin: (c) PABP promoter (human poly(A)-binding protein promoter) and (d) S16 promoter (mouse ribosomal protein (rp) S16 promoter). Transfection studies showed that, irrespective of promoter type, large (> or =500 nm) MLV were superior to approximately 100 nm LUV; the extent of superiority was dependent on liposome lipid composition (larger for 100% DOTAP and DOTAP/DOPE than for DOTAP/DOPC and DOTAP/cholesterol). The optimal DNA(-)/DOTAP(+) charge ratio for all types of lipoplexes used was 0.2 or 0.5 (namely, when the lipoplexes were positively charged). Scoring the six best lipoplex formulations (out of 128 studied) revealed the following order: pCMV (DOTAP/DOPE) >> pSV (DOTAP/DOPE)=pCMV(DOTAP/cholesterol)=pS16 (100% DOTAP)=pS16 DOTAP/DOPE >> pCMV (DOTAP/DOPC). The lack of trivial consistency in the transfection efficiency score, the pattern of transfection efficiency, and statistical analysis of the data suggest that there is cross-talk between promoter type and lipoplex lipid composition, which may be related to the way the promoter is associated with the lipids.

3T3 Cells↗
PubMed1983

Reverse transcriptase and its associated ribonuclease H: interplay of two enzyme activities controls the yield of single-stranded complementary deoxyribonucleic acid.

The synthesis of single-stranded globin cDNA by the RNA-directed DNA polymerase activity of reverse transcriptase in the presence of oligothymidylate primers was investigated in order to determine the limitations to higher yields. The results indicated that the associated ribonuclease H activity, an integral part of reverse transcriptase, plays a large role in the synthesis of the first strand of cDNA and that the interplay of the two enzyme activities for any specific set of conditions determines the yield of single-stranded products. In both the presence and the absence of polymerization, the associated ribonuclease H catalyzed the deadenylation of mRNA, producing molecules that were somewhat shorter, highly homogeneous in size, and fully translatable into globin protein. They were also entirely lacking in the ability to serve as templates for cDNA synthesis. The reaction was completely dependent on oligothymidylate and completely independent of deoxyribonucleoside triphosphates. The initial rate of deadenylation was one-fourth the initial rate of initiation of polymerization when saturating levels of deoxyribonucleoside triphosphates were used in the polymerase reaction. In the presence of ribonuclease H activity, the DNA polymerase catalyzed the synthesis of an array of cDNAs including some that were full length. The initiation of polymerization was rate limiting: once synthesis had begun, it required 1-1.5 min to transcribe globin mRNA. However, most primers that were elongated were aborted prematurely. Maximum synthesis of full-length cDNA required stoichiometric levels of enzyme and high triphosphate levels, but regardless of conditions, the sum of completed cDNA and deadenylated mRNA accounted for only 50% of the input mRNA. The data fit a model in which synthesis of full-length cDNA molecules depends on the arrangement of primers and transcription initiation complexes on the poly(A) "tail" of mRNA.

Animals↗
PubMed2001

Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators. ER selective ligands.

Analysis of estrogen receptor alpha and beta interplay with other transcription factors is critical to the understanding of how small molecules, the cognate ligands for these receptors, selectively regulate the mode and amplitude of gene transcription by affecting receptor activity. To better understand the molecular mechanisms of selective action of estrogen receptor ligands, we characterized estrogen receptor alpha and beta (ER) interaction with the p160 family of coactivators. We also investigated how these interactions are affected by binding of specific ligands. We show that ER alpha and beta utilize different LXXLL motifs for their interaction with p160 family members. We found that significant differences exist between the affinity of the nuclear receptor interacting domain (NRID) and interaction of separate LXXLL motifs with ERs. This result indicates that a single LXXLL motif is unlikely to be sufficient for interaction with receptors, and that regions other than LXXLL motifs also participate in ER-p160 complex formation. We found that ER alpha and beta have strong affinity preferences for particular coactivators. These results suggest that ER-mediated transcription is not driven by a random mixture of ER-coactivator complexes. We also show that some ER ligands are functionally specific. We describe a ligand that binds to both receptors, but enhances only ER beta interaction with SRC1 and SRC3 while exhibiting little effect on the ER alpha interaction with these proteins. Finally, we provide data that suggest how genistein may selectively recruit coactivators when liganded to ERs. It enhances the interaction of ERs with SRC1 and SRC3, but demonstrates a minimal effect on receptor interaction with DRIP205 and CBP.

Acetyltransferases↗
PubMed1998

Interplay between S1 and S4 subsites in Kex2 protease: Kex2 exhibits dual specificity for the P4 side chain.

The yeast Kex2 protease is the prototype of a family of eukaryotic proprotein processing proteases that includes PC1, PC2, and furin. The catalytic domains of these enzymes are homologous to the degradative serine proteases of the subtilisin family. Kex2 exhibits optimal activity toward substrates with Lys or Arg at P2 and Arg at P1 (Lys-Arg or Arg-Arg cleavage sites). However, mammalian proprotein processing proteases such as furin exhibit more stringent requirements for basic residues at P4 than at P2. Here we demonstrate that Kex2 protease also recognizes P4, with dual specificity for aliphatic and basic residues. Recognition of P4 is even more readily apparent in substrates having a poor P1 residue (Lys). Kinetic analysis of a series of otherwise identical fluorogenic substrates with Lys at P1 and different residues at P4 indicates that large, aliphatic P4 residues increase kcat/KM by 100-fold. However, smaller residues or acidic residues at P4 do not. P4 Arg also confers efficient cleavage on such a substrate, but the uncharged isostere of Arg, citrulline, does not. Kex2 may thus possess distinct subsites that recognize aliphatic or basic P4 side chains. Although a favorable P4 residue can partially compensate for the defects in kcat and kcat/KM seen with Lys in place of Arg at P1, this substitution resulted in a change in rate-determining step for all substrates examined. As previously seen in the case of subtilisin, effects of substitutions at the P1 and P4 positions were not independent, suggesting that interplay between these two positions is a common feature of substrate specificity for both processing proteases and degradative enzymes of the subtilisin superfamily.

Amino Acid Sequence↗
PubMed2000

Interplay between folding/unfolding and helix/coil transitions in giant DNA.

It has been well established that double-stranded DNA undergoes a melting, or helix/coil, transition into a single-stranded coil state with an increase in temperature. On the other hand, it has recently been found that, at a fixed temperature, long DNA, larger than several kilobase pairs, exhibits a discrete transition, or switching, between elongated and folded states, preserving its double-stranded structure, with the addition of various condensation agents, such as alcohol, hydrophilic polymer, multivalent cation, and cationic surfactant. In the present study, we examined the interplay between the folding/unfolding transition and the helix/coil transition in individual giant DNA molecules, by observing the conformation of single molecular chains with fluorescence microscopy. The results indicate that the helix-to-coil transition tightly cooperates with the unfolding transition in DNA.

Circular Dichroism↗