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At least 253 records · Page 14Linked to original sources

Effects of the major metabolite of phencyclidine, the trans isomer of 4-phenyl-4-(1-piperidinyl)cyclohexanol, on [3H]N-(1-[2-thienyl] cyclohexyl)-3,4-piperidine ([3H]TCP) binding and [3H]dopamine uptake in the rat brain.

The major metabolite of phencyclidine (PCP), the trans isomer of 4-phenyl-4-(1-piperidinyl)cyclohexanol [(trans)-4-PPC], inhibited [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical membranes with much less activity than PCP itself. In contrast, it inhibited [3H]dopamine ([3H]DA) uptake in rat striatal synaptosomes to a similar extent as PCP. Considering our previous observations that intraperitoneally administered (trans)-4-PPC elicits dose-related increases in locomotor activity and rearing in mice, (trans)-4-PPC as well as PCP may be involved in psychotomimetic effects of PCP due to its inhibitory effect on DA uptake.

Animals↗

Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an alpha-TCP paste.

The development of the new technologies of bone tissue engineering requires the production of bioresorbable macroporous scaffolds. Calcium phosphate cements are good candidate materials for the development of these scaffolds, as an alternative to the traditional porous sintered ceramics. In this work a novel two-step method, based in the foaming of an alpha-tricalcium phosphate (alpha-TCP) cement paste and its subsequent hydrolysis to a calcium deficient hydroxyapatite (CDHA) is presented. The foaming agent was a hydrogen peroxide (H2O2) solution, which decomposes in water and oxygen gas. CDHA foams, which combined an interconnected macroporosity with a high microporosity were obtained. The apatitic phase obtained by the hydrolysis reaction was more similar to the biologic one, in terms of chemical composition, crystallinity and specific surface than the hydroxyapatites obtained by sintering. The percentage of porosity in the foams reached a 66%. It was shown that it was possible to control the porosity, and pore size and shape by different processing parameters such as the liquid-to-powder ratio, the concentration of the H2O2 solution and the particle size of the powder.

Biocompatible Materials↗

4,5,9,10-Tetrahydro-1,4-ethanobenz[b]quinolizine as a prodrug for its quinolizinium cation as a ligand to the open state of the TCP-binding site of NMDA receptors.

A new derivative of 4,5,9,10-tetrahydro-1,4-ethanobenz[b]quinolizine (2) has been designed as a prodrug for its quinolizinium cation (1) that is a potent antagonist of the TCP-binding site of NMDA receptors at the open state. The 11C-labeled 2 showed high accumulation of radioactivity in the brain in an in vivo biodistribution study. The speculation of 2 as a prodrug of 1 has been proven by the fact that 1 was observed in a high ratio to 2 in an analysis by RP-HPLC of the brain homogenates.

Animals↗

Expression of three t-complex genes, Tcp-1, D17Leh117c3, and D17Leh66, in purified murine spermatogenic cell populations.

Transmission ratio distortion (TRD) is a property of the complete t-haplotype which results in the preferential transmission of the t-haplotype chromosome from heterozygous t/+ males to the majority of the progeny. Available data suggest that in t/+ males, a dysfunction of the wild-type sperm within the female reproductive tract is responsible for the observed deviation from Mendelian segregation ratios. Genetically, Lyon has shown that multiple loci within the t-complex are required for maximum levels of TRD. These loci include multiple t-complex distorters (Tcds) which act upon a single t-complex responder (Tcr). Testis-expressed genes have been cloned which map to the same subregions of the t-complex as the Tcds and Tcr and are thus considered candidate genes for the products of these loci. To begin to understand how the products of these loci biochemically control TRD, the expression of three TRD-candidate genes (Tcp-1, D17Leh117c3, and D17Leh66) has been determined in populations of spermatocytes and differentiated spermatids purified to near homogeneity by unit gravity sedimentation. Fractions covering the entire gradient were analysed resulting in a more accurate picture of the precise timing of expression than previously reported. Transcription of all three genes was up-regulated in pachytene primary spermatocytes and persisted at stable levels through the haploid spermatid stages. Significantly, only levels of mRNA encoded by D17Leh66, the candidate gene for Tcr, increased from early round to elongating-stage spermatids. If this pattern of expression does, in fact, represent Tcr, these data provide the first direct evidence that wild-type and t-haplotype Tcr elements could be differentially expressed in haploid spermatids.

Animals↗

Internal telomeric repeats and 'TCP domain' protein-binding sites co-operate to regulate gene expression in Arabidopsis thaliana cycling cells.

We have focused our interest on two cis-regulatory elements, named site II motif and telo box, identified within the promoter of plant proliferating cellular nuclear antigen (PCNA) and putatively involved in meristematic expression of the gene. A conserved topological association between site II motifs and telo boxes is observed in the promoter of numerous genes expressed in cycling cells, including several cell cycle-related genes and 153 Arabidopsis genes encoding ribosomal proteins. Meristematic expression of a GUS reporter gene was observed in plants under the control of Arabidopsis site II motif within a minimal promoter. This expression is strongly enhanced by addition of a telo box within this chimaeric promoter. We showed by gel retardation experiments that the site II motif is a target for several DNA-binding activities present in Arabidopsis crude cell extract and can bind a transcription factor, At-TCP20, from the Teosinte branched 1, Cycloidea, PCF (TCP)-domain protein family. In yeast two-hybrid experiments, At-TCP20 appears to be a potential partner of AtPuralpha, which was previously shown to bind telo boxes. An important consequence of this analysis is to reveal new and conserved regulatory processes concerning the regulation of plant ribosomal gene expression in cycling cells. The implication of these observations in plant-specific developmental pathways is discussed.

Arabidopsis↗

Floral asymmetry involves an interplay between TCP and MYB transcription factors in Antirrhinum.

To understand how genes control floral asymmetry, we have isolated and analyzed the role of the RADIALIS (RAD) gene in Antirrhinum. We show that the RAD gene encodes a small MYB-like protein that is specifically expressed in the dorsal region of developing flowers. RAD has a single MYB-like domain that is closely related to one of the two MYB-like domains of DIV, a protein that has an antagonistic effect to RAD on floral development. Interactions between RAD and other genes indicate that floral asymmetry depends on the interplay between two pairs of transcription factors. First, a pair of TCP proteins is expressed in dorsal regions of the floral meristem, leading to the activation of RAD in the dorsal domain. The RAD MYB-like protein then antagonizes the related DIV MYB-like protein, preventing DIV activity in dorsal regions. In addition to its role in dorsal regions, RAD acts nonautonomously on lateral regions either directly, through RAD protein movement, or indirectly, through a signaling molecule.

Amino Acid Sequence↗

Limitations of a TCP model incorporating population heterogeneity.

The variation between individuals in their dose-response characteristics complicates attempts to extract estimates of radiobiological parameters (e.g. alpha, beta, etc) from fits to clinical dose-response data. The use of 'population' dose-response models that explicitly account for this variability is necessary to avoid obtaining skewed parameter estimates. In this work, we evaluated an example of a 'population' tumour control probability (TCP) model in terms of its ability to provide reliable parameter estimates. This was accomplished by performing fits of this population model to 'pseudo' data sets, which were generated with Monte Carlo techniques and based on preset values for the various radiobiological parameters. The fitting exercises illustrated considerable correlations between the model parameters. Especially significant was the large correlation observed between the parameter mu=alpha/sigmaalpha used to characterize the level of population heterogeneity in radiosensitivity and the alpha/beta parameter typically used to describe the response to fractionation. The results imply that fits to clinical data may not be able to distinguish between tumours exhibiting a high degree of heterogeneity and a strong beta-mechanism and those containing little heterogeneity and having a weak beta-mechanism. One implication is that basing the design of optimal fractionation regimes on such fitting results may be error-prone. If in vitro assays are to be used to independently determine biologically reasonable ranges for parameter values, an accurate knowledge of the relationship between in vitro and in vivo dose-response characteristics is required.

Animals↗

Processing of TCP pilin by TcpJ typifies a common step intrinsic to a newly recognized pathway of extracellular protein secretion by gram-negative bacteria.

Biogenesis of the Vibrio cholerae toxin-coregulated pilus (TCP) requires the activities of at least seven accessory proteins. We demonstrate that a portion of this pathway involves a novel processing step in which a hydrophilic leader peptide is proteolytically removed from TcpA by the gene product characterized in this report, TcpJ, to yield the mature, export-competent form of the pilin. Cleavage of the pilin leader peptide is independent of known signal peptidases as demonstrated by pilin-processing profiles in Escherichia coli strains conditionally defective for production of leader peptidase or grown in the presence of the antibiotic globomycin. Additionally, pilin cleavage did not rely on the SecA protein, as evidenced by TcpA processing in azide-treated cells. These results suggest that TcpJ is representative of a new class of proteins involved in SecA-independent proteolytic cleavage of a set of atypical leader peptides during extracellular export.

Amino Acid Sequence↗

Differential expression of the Arabidopsis cytochrome c genes Cytc-1 and Cytc-2. Evidence for the involvement of TCP-domain protein-binding elements in anther- and meristem-specific expression of the Cytc-1 gene.

The promoters of the Arabidopsis (Arabidopsis thaliana) cytochrome c genes, Cytc-1 and Cytc-2, were analyzed using plants transformed with fusions to the beta-glucuronidase coding sequence. Histochemical staining of plants indicated that the Cytc-1 promoter directs preferential expression in root and shoot meristems and in anthers. In turn, plants transformed with the Cytc-2 promoter fusions showed preferential expression in vascular tissues of cotyledons, leaves, roots, and hypocotyls, and also in anthers. Quantitative measurements in extracts prepared from different organs suggested that expression of Cytc-1 is higher in flowers, while that of Cytc-2 is higher in leaves. The analysis of a set of deletions and site-directed mutants of the Cytc-1 promoter indicated that a segment located between -147 and -156 from the translation start site is required for expression and that site II elements (TGGGCC/T) located in this region, coupled with a downstream internal telomeric repeat (AAACCCTAA), are responsible for the expression pattern of this gene. Proteins present in cauliflower nuclear extracts, as well as a recombinant protein from the TCP-domain family, were able to specifically bind to the region required for expression. We propose that expression of the Cytc-1 gene is linked to cell proliferation through the elements described above. The fact that closely located site II motifs are present in similar locations in several genes encoding proteins involved in cytochrome c-dependent respiration suggests that these elements may be the target of factors that coordinate the expression of nuclear genes encoding components of this part of the mitochondrial respiratory chain.

Arabidopsis↗

A group of TCP transcription factors is a missing link in strigolactone signaling.

Strigolactones (SLs) are plant-specialized butenolide signaling molecules, recognized as endogenous plant hormones, that control plant development and environmental adaptation. In Arabidopsis (Arabidopsis thaliana), the repressor D53-like SMXLs regulate the expression of a vast number of genes in an EAR-motif-dependent manner to mediate SL signaling. However, it remains unclear how the SMXLs are recruited to specific genes and implement unique functions in vivo. Based on chromatin co-distribution analysis, we constructed a chromatin co-localization map of SMXL6 with 108 transcription factors. Among the candidate transcription factors, the Class II TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) family member TCP4 shows the highest frequency of chromatin co-localization with SMXL6. SMXL6 and TCP4 co‑localize at the promoter regions of 18 SL-induced SMXL6 target genes (SISGs), including BRC1. We confirmed that TCP4 interacts with SMXL6 and can bind directly to these co‑localized sites. The loss of CIN-TCPs function reduces the hormone responsiveness of the SL-induced genes. Introducing the tcp3/4/10 into SL‑deficient mutants restored the BRC1 expression to a level exceeding that of the wild type. However, the branching phenotype of the SL‑deficient mutant was only partially rescued, suggesting a limited role for BRC1 in SL‑mediated branching control and implicating the involvement of additional factors. An unexpected finding was that tcp3/4/10 rescued the dwarf phenotype of the SL‑deficient mutants, providing an opportunity to elucidate the mechanisms underlying SL‑regulated plant height. These findings demonstrate that TCP4 mediates SMXL6 chromatin recruitment during SL signaling, and provide a new understanding of how SMXL6 participates in SL signaling-mediated gene expression and plant development.

Lactones↗

The yeast homolog to mouse Tcp-1 affects microtubule-mediated processes.

A Saccharomyces cerevisiae homolog to Drosophila melanogaster and mouse Tcp-1 encoding tailless complex polypeptide 1 (TCP1) has been identified, sequenced, and mapped. The mouse t complex has been under scrutiny for six decades because of its effects on embryogenesis and sperm differentiation and function. TCP1 is an essential gene in yeast cells and is located on chromosome 4R, linked to pet14. The TCP1-encoded proteins in yeast, Drosophila, and mouse cells share between 61 and 72% amino acid sequence identities, suggesting a primordial function for the TCP1 gene product. To assess function, we constructed a cold-impaired recessive mutation (tcp1-1) in the yeast gene. Cells carrying the tcp1-1 mutation grew linearly rather than exponentially at the restrictive temperature of 15 degrees C with a generation time of approximately 32 h in minimal medium. Both multinucleate and anucleate cells accumulated with time, suggesting that the linear growth kinetics may be explained by the generation of anucleate buds incapable of further cell division. In addition, the multinucleate and anucleate cells contained morphologically abnormal structures detected by anti-alpha-tubulin antibodies. The kinetics of appearance of these abnormalities suggest that they are a direct consequence of loss of function of the TCP1 protein and not a delayed, indirect consequence of cell death. We also observed that strains carrying tcp1-1 were hypersensitive to antimitotic compounds. Taken together, these observations imply that the TCP1 protein affects microtubule-mediated processes.

Amino Acid Sequence↗

The effectiveness of RA wrist fusion using Beta-TCP without autogenous iliac bone grafting: a report of four cases.

Wrist arthrodesis is indicated for the rheumatoid hand especially in cases with severe destruction of the carpal bones. In the arthrodesis procedure for the rheumatoid wrist, autogenous iliac bone grafting is required in most cases. However, autogenous iliac bone graft necessitates the additional surgical intervention, and can be associated with the problem of inadequate bony quality or quantity. It is thought that use of the artificial bone substitute in the procedure can lessen the surgical morbidity while supplying the consistent material without shortage of graft quantity. We have performed arthrodesis of the rheumatoid wrist using beta-TCP for four patients. Clinical results of these patients were satisfactory both in pain relief and functional improvement with complete bony healing. Therefore, this procedure seems to be an effective option for the rheumatoid wrist with severe destructive changes.

Arthritis, Rheumatoid↗

Dispersive X-ray Spectroscopy Analysis of Porous beta-TCP Bioceramics after Implantation into Femur.

In this paper, energy dispersive X-ray spectroscopy and element ratio of implanted bioceramic, interface and rabbit femur when the bioceramic implanted into femur were measured by two different scan electron microscopy (SEM) EDXA modes. The changes of element ratio and components of materials and interface implanted into femur were compared. Thorough studies were made on the transformation of TCP from lifeless materials into living bones after implantation, by using SEM-EDXA, Raman spectra and infrared spectra. These results provided rich evidence for understanding biodegration and bone bonding mechanism of calcium phosphate bioceramics.

Journal Article↗

TCP and NTCP: a basic introduction.

Radiotherapy is one of the most effective treatments for cancer. The aim of radiotherapy is to achieve a high probability of local tumor control (tumor control probability, TCP) at a low risk of normal tissue complications (normal tissue complication probability, NTCP). This paper gives a brief introduction into dose response relationships for early and late radiation responses and tumor control. The impact of basic parameters of the fractionation schedules on these responses is described. Easy examples illustrate how Poisson statistics can be used to understand dose-response relationships in radiotherapy.

Dose Fractionation, Radiation↗

Evaluation of lining materials and a new concept for lining: alpha-TCP cement or visible light curing calcium hydroxide composition in composite resin restoration.

Histological studies on the effect of lining methods using a alpha-TCP (TC) and a VLC Dycal (LD) were reported previously. In this report, SEM and electron-probe microanalyzer observations were utilized to determine the effects of lining methods. SEM observations were made on longitudinal sections prepared by a freeze fracture method, using 30 vital dog teeth and 5 vital human teeth. In the LD group, several kinds of crystal growth were seen on surfaces of the material and dentinal wall. In the TC group, the exfoliated space area filled up with rod-shaped crystals. An electron-probe microanalyzer was employed to examine the crystal elements observed in the interface or the exfoliated space area. Our findings indicated that lining appeared to fill the gaps with crystal growth, block stimuli which result from bacterial invasion into the dentinal tubules, and reinforce the superficial dentinal zone.

Acid Etching, Dental↗

Quantitation of two-dimensional gel proteins reveals unequal amounts of Tcp-1 gene products during mouse spermatogenesis but no correlation with transmission ratio distortion.

The discovery of a protein, p63/6.9, that is synthesized by both somatic and germ cells and coded for by a gene, Tcp-1, within the t complex provides a molecular probe for examining transmission ratio distortion in t mice. Two electromorphs of this protein exist. The acidic protein (a) is encoded by t-haplotype chromosomes, while the basic protein (b) is encoded by wild-type 17th chromosomes. We have measured the relative amounts of p63/6.9a and p63/6.9b for various t-complex bearing males and for several stages of spermatogenesis. There was no correlation between the ratio of p63/6.9a to b and the magnitude of transmission ratio distortion but the relative amounts of these proteins present in testicular cells can vary depending on the method of labelling. In vivo labelling results in the detection of two-fold greater amounts of p63/6.9a while in vitro labelling produces equimolar amounts of these two proteins. These data suggest that unequal synthesis or degradation of the p63/6.9 proteins occurs during spermatogenesis. It is proposed that increased synthesis of p63/6.9a in vivo is an intrinsic property of t-haplotypes.

Animals↗

Identification of the major chromaffin granule-binding protein, chromobindin A, as the cytosolic chaperonin CCT (chaperonin containing TCP-1).

Chromobindin A is a multisubunit complex ATPase that binds to chromaffin granule membranes in a calcium-dependent manner and requires ATP for release from the membrane (Martin, W. H., and Creutz, C. E. (1987) J. Biol. Chem. 262, 2803-2810). Here we report that the seven previously characterized subunits of chromobindin A cross react with antisera specific to subunits of CCT, the chaperonin containing TCP-1 (Kubota, H., Hynes, G., Carne, A., Ashworth, A., and Willison, K. (1994) Curr. Biol. 4, 89-99). The chromobindin A subunits previously called chromobindins 12, 13, 14, 15, 16, 18, and 19 cross-react specifically with subunits beta, delta, theta, alpha, zeta, xi, and gamma, respectively, of CCT. Additional similarities in subunit molecular weights, isoelectric points, and the morphologies of the two protein complexes as determined by electron microscopy support identification of chromobindin A as an adrenal medullary form of CCT. The chromobindin A/CCT complex was found to bind at least 7-fold more efficiently to affinity columns of chromaffin granule membranes than of adrenal medullary cytosol proteins, suggesting a specific interaction occurs between the complex and membrane components. The results indicate that the previously described characteristics of chromobindin A are likely to be relevant to the functions of CCT and suggest that the adrenal medullary form of CCT may play a role in the activities of secretory vesicle membranes.

Animals↗

Review: nucleotide-dependent conformational changes of the chaperonin containing TCP-1.

Current biochemical and structural studies on the conformational changes induced by the nature of nucleotide bound to the chaperonin containing testis complex polypeptide 1 (CCT) are examined to see how consistent the data are. This exercise suggests that the biochemical and structural data are in good agreement. CCT clearly appears as a folding nano-machine fueled by ATP. A careful comparison of the biochemical and structural data, however, highlights a number of points that remain to be carefully documented in order to better understand the nature of the conformational changes in CCT that yield folded target proteins. Special effort should be made to clearly answer the points listed at the end of this review in order to obtain the dynamic sequence of events yielding folded proteins in the eukaryotic cytoplasm similar to what has been obtained for prokaryotes.

Adenosine Triphosphate↗