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C C Martin

Publications and source records attributed to C C Martin.

At least 19 recordsLinked to original sources
PubMed2004

Identification and characterization of a cDNA and the gene encoding the mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein.

Glucose-6-phosphatase (G6Pase) catalyzes the final step in the gluconeogenic and glycogenolytic pathways, the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate. This paper describes the identification and characterization of a cDNA and the gene encoding the mouse ubiquitously expressed G6Pase catalytic subunit-related protein (UGRP). The open reading frame of this UGRP cDNA encodes a protein (346 amino acids (aa); Mr 38,755) that shares 36% overall identity (56% similarity) with the mouse G6Pase catalytic subunit (357 aa; Mr 40,454). UGRP exhibits a similar predicted transmembrane topology and conservation of many of the catalytically important residues with the G6Pase catalytic subunit; however, unlike the G6Pase catalytic subunit, UGRP does not catalyze G6P hydrolysis and does not contain a carboxy-terminal di-lysine endoplasmic reticulum retention signal. UGRP mRNA was detected by RNA blot analysis in every mouse tissue examined with the highest expression in heart, brain, testis and kidney. Database analysis showed that the mouse UGRP gene is composed of six exons, spans approximately 4.2 kbp of genomic DNA and is located on chromosome 11 along with the G6Pase catalytic subunit gene. The UGRP gene transcription start sites were mapped by primer extension analysis, and the activity of the mouse UGRP gene promoter was analyzed using luciferase fusion gene constructs. In contrast to the G6Pase catalytic subunit gene promoter, the UGRP promoter was highly active in all cell lines examined.

Amino Acid Sequence↗
PubMed2002

Identification and characterization of a human cDNA and gene encoding a ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein.

Glucose-6-phosphatase (G6Pase) catalyzes the final step in the gluconeogenic and glycogenolytic pathways, the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate. This paper describes the identification and characterization of a human cDNA and gene encoding a ubiquitously expressed G6Pase catalytic subunit-related protein (UGRP). The ORF of this UGRP cDNA encodes a protein (346 amino acids (aa); M(r) 38 709) which shares 36% overall identity to the human G6Pase catalytic subunit (357 aa; M(r) 40 487). UGRP exhibits a similar predicted transmembrane topology and conservation of many of the catalytically important residues with the G6Pase catalytic subunit; however, unlike the G6Pase catalytic subunit, UGRP does not catalyze G6P hydrolysis. UGRP mRNA was detected by RNA blot analysis in every tissue examined with the highest expression in muscle. Database analysis showed that the human UGRP gene is composed of six exons, spans approximately 5.4 kbp of genomic DNA and is located on chromosome 17q21 with the G6Pase catalytic subunit gene. The UGRP gene transcription start sites were mapped by primer extension analysis, and the activity of the UGRP gene promoter was analyzed using luciferase fusion gene constructs. In contrast to the G6Pase catalytic subunit gene promoter, the UGRP promoter was highly active in all cell lines examined.

Amino Acid Sequence↗
PubMed2001

Cloning and characterization of the human and rat islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) genes.

Islet-specific glucose-6-phosphatase (G6Pase) catalytic subunit-related protein (IGRP) is a homolog of the catalytic subunit of G6Pase, the enzyme that catalyzes the terminal step of the gluconeogenic pathway. Its catalytic activity, however, has not been defined. Since IGRP gene expression is restricted to islets, this suggests a possible role in the regulation of islet metabolism and, hence, insulin secretion induced by metabolites. We report here a comparative analysis of the human, mouse, and rat IGRP genes. These studies aimed to identify conserved sequences that may be critical for IGRP function and that specify its restricted tissue distribution. The single copy human IGRP gene has five exons of similar length and coding sequence to the mouse IGRP gene and is located on human chromosome 2q28-32 adjacent to the myosin heavy chain 1B gene. In contrast, the rat IGRP gene does not appear to encode a protein as a result of a series of deletions and insertions in the coding sequence. Moreover, rat IGRP mRNA, unlike mouse and human IGRP mRNA, is not expressed in islets or islet-derived cell lines, an observation that was traced by fusion gene analysis to a mutation of the TATA box motif in the mouse/human IGRP promoters to TGTA in the rat sequence. The results provide a framework for the further analysis of the molecular basis for the tissue-restricted expression of the IGRP gene and the identification of key amino acid sequences that determine its biological activity.

Amino Acid Sequence↗
PubMed2001

A tool for comparison of PET and fMRI methods: calculation of the uncertainty in the location of an activation site in a PET image.

A technique for calculating the uncertainty in the location of an activation site in a PET image, without performing repeated measures, is presented. With the development of new fMRI methods for measuring cerebral hemodynamics, demonstration of the efficacy of these techniques will be critical to establish clinical utility. Comparisons with PET are a powerful tool for validating these new fMRI techniques. In addition to the fact that PET techniques are well-established methods for making physiological measurements in vivo, PET methods are also free of the geometric distortions and nonuniform signal-to-noise artifacts (due to signal dropout) common in fMRI techniques. Comparisons reported previously have been limited by the large number of trials acquired in single-subject fMRI studies and the small number of trials in a PET study (due to the radiation dose to the patient or the interscan delays for tracer decay). Our method calculates both the center of mass (CM) of a predefined region of interest and the uncertainty in the location of the CM using the preimage PET data (sinograms). Results of phantom studies demonstrate that our method is an unbiased measurement equivalent to that of repeated measures with a large number of images. Extension of this technique to estimate the uncertainty in the location of an activation site in a PET statistical parametric map will permit precise rigorous comparisons of PET and fMRI methods in single subjects without the constraints imposed by the relatively small number of PET measurements.

Brain Mapping↗
PubMed2001

Expression of the chaperonin 10 gene during zebrafish development.

We have isolated a cDNA encoding chaperonin 10 (cpn10) from the zebrafish. Using northern, western, and in situ hybridization analysis, we observed that the cpn10 gene is expressed uniformly and ubiquitously throughout embryonic development of the zebrafish. Upregulation of cpn10 expression was observed following exposure of zebrafish embryos to a heat shock of 1 hour at 37 degrees C compared to control embryos raised at 27 degrees C. The extracellular form of Cpn10 called early pregnancy factor (EPF), found in the serum of pregnant mammals, was not detected in the serum of either male or female zebrafish. These expression studies suggest that Cpn10 plays a general role in zebrafish development as well as being consistent with the hypothesis that EPF is involved in the embryo implantation process in mammals.

Animals↗
PubMed2001

[Exhumations procedures for investigating the genetic link in bones].

OBJECTIVE: To identify technical problems in exhumations performed for DNA detection in bones and to propose solutions through a protocol. METHODS: A prospective and qualitative study of exhumations was carried out according to the methods proposed in the medical legal literature. From 1995 to 1998, were performed 10 exhumations to collect human remains for DNA extraction. Of them, seven cases were of civil interest and three of criminal. Alternatives were sought to overcome technical difficulties found during the execution of these procedures. RESULTS: For all cases, there was scarcity of useful information to identify the human remains. In half of them, identification was based on the individual's morphological characteristics, given by their relatives. Individual morphological characteristics contributed to identification in 50% of cases. In three cases, it was possible to determine only the sex, and in one of them, only the age. Lack of infrastructure and police security in the cemeteries impaired the examination. CONCLUSIONS: To assure the reliability of the DNA molecular examination, it is necessary to identify the individual to whom the exhumed mortal remains belonged. To an efficacious investigation, it is paramount to have a working protocol that will cover, among other issues, those concerning identification, infrastructure and staff safety at the site of examination.

Adolescent↗
PubMed2001

Characterization of the mouse islet-specific glucose-6-phosphatase catalytic subunit-related protein gene promoter by in situ footprinting: correlation with fusion gene expression in the islet-derived betaTC-3 and hamster insulinoma tumor cell lines.

Glucose-6-phosphatase (G6Pase) is a multicomponent system located in the endoplasmic reticulum comprising a catalytic subunit and transporters for glucose-6-phosphate, inorganic phosphate, and glucose. We have recently cloned a novel gene that encodes an islet-specific G6Pase catalytic subunit-related protein (IGRP) (Ebert et al., Diabetes 48:543-551, 1999). To begin to investigate the molecular basis for the islet-specific expression of the IGRP gene, a series of truncated IGRP-chloramphenicol acetyltransferase (CAT) fusion genes were transiently transfected into the islet-derived mouse betaTC-3 and hamster insulinoma tumor cell lines. In both cell lines, basal fusion gene expression decreased upon progressive deletion of the IGRP promoter sequence between -306 and -66, indicating that multiple promoter regions are required for maximal IGRP-CAT expression. The ligation-mediated polymerase chain reaction footprinting technique was then used to compare trans-acting factor binding to the IGRP promoter in situ in betaTC-3 cells, which express the endogenous IGRP gene, and adrenocortical Y1 cells, which do not. Multiple trans-acting factor binding sites were selectively identified in betaTC-3 cells that correlate with regions of the IGRP promoter identified as being required for basal IGRP-CAT fusion gene expression. The data suggest that hepatocyte nuclear factor 3 may be important for basal IGRP gene expression, as it is for glucagon, GLUT2, and Pdx-1 gene expression. In addition, binding sites for several trans-acting factors not previously associated with islet gene expression, as well as binding sites for potentially novel proteins, were identified.

Animals↗
PubMed1999

Assessment of methods of homicides in a Brazilian city: a preliminary study.

Homicides in the city of Ribeirão Preto, state of São Paulo, Brazil, were analyzed with regard to methods (firearms or others) and gender, in a retrospective study from 1993 to 1997. There was a progressive increase in the number of homicides, mainly after 1995, with an increment of 86.6% in 1997 in comparison to 1993. The incidence of homicides was higher among males, with firearms being the most common method in this group since 1993. In addition, a 10% increase in this method was observed since 1995, in association with a proportional reduction in the use of other methods. The incidence of homicides among females remained stable until 1996 and increased by 51.3% in 1997. Simultaneously, firearms have become the most common method among female victims (71.4%), pattern similar to that observed among males. Attention is drawn to the social and economic conditions and their relationships with drug traffic in the city.

Adolescent↗
PubMed1999

Disruption of zebrafish somite development by pharmacologic inhibition of Hsp90.

Members of the Hsp90 family of molecular chaperones play important roles in allowing some intracellular signaling molecules and transcription factors to reach and maintain functionally active conformations. In the present study, we have utilized the specific Hsp90-binding agent, geldanamycin, to examine the requirement for Hsp90 during zebrafish development. We show that geldanamycin interacts with both the alpha and the beta-isoforms of zebrafish Hsp90 and that geldanamycin-treated embryos consistently exhibit a number of defects in tissues which express either one of these genes. Within the somites, geldanamycin treatment results in the absence of eng-2-expressing muscle pioneer cells. However, early development of adaxial cells, which give rise to muscle pioneers and which strongly express the hsp90alpha gene shortly before muscle pioneer formation, appeared unaffected. Furthermore, development of the notochord, which provides many of the signals required for proper somite patterning and which does not express detectable levels of either hsp90alpha or hsp90beta mRNA, was similarly unaffected in geldanamycin-treated embryos. The data are consistent with there being a temporal and spatial requirement for Hsp90 function within somitic cells which is necessary for the formation of eng-2-expressing muscle pioneers and possibly other striated muscle fiber types.

Animals↗
PubMed1999

A role for DNA methylation in gastrulation and somite patterning.

DNA methylation constitutes an important epigenetic factor in the control of genetic information. In this study, we analyzed expression of the DNA methyltransferase gene and examined DNA methylation patterns during early development of the zebrafish. Maternal transcripts of the zebrafish DNA methyltransferase gene (MTase) are ubiquitously present at high levels in early embryos with overall levels decreasing after the blastula stage. At 24 h, methyltransferase mRNA is predominantly found in the brain, neural tube, eyes, and differentiating somites. Expression of MTase in the somites is highest in the anterior cells of the somites. Despite the high levels of MTase mRNA in blastula-stage embryos, we observe DNA hypomethylation at the blastula and gastrula stages compared to sperm or older embryos. Zebrafish embryos treated with 5-azacytidine (5-azaC) and 5-aza-2-deoxycytidine (5-azadC), nucleotide analogs known to induce cellular differentiation and DNA hypomethylation in mammalian cells, exhibit DNA hypomethylation and developmental perturbations. These defects are specifically observed in embryos treated at the beginning of the blastula period, just prior to midblastula transition. The most common phenotype is the loss of tail and abnormal patterning of somites. Head development is also affected in some embryos. Histological and in situ hybridization analyses reveal whole or partial loss of a differentiated notochord and midline muscle in treated embryos. When examined during gastrulation, 5-azaC-treated embryos have a shortened and thickened axial mesoderm. We propose that DNA methylation is required for normal gastrulation and subsequent patterning of the dorsal mesoderm.

Abnormalities, Drug-Induced↗
PubMed1999

Effect of partition coefficient, permeability surface product, and radioisotope on the signal-to-noise ratio in PET functional brain mapping: a computer simulation.

In this work we use a computer simulation to estimate the magnitude of improvement in the signal-to-noise ratio of PET functional brain mapping studies as a function of partition coefficient and permeability surface product for O-14, F-17, and O-15 labeled flow tracers. A model for signal-to-noise ratio is derived from the Kety model for inert diffusible blood flow tracers. The results of the simulation suggest that moderate increases in partition coefficient and permeability surface product compared with water would lead to an increase in signal-to-noise ratio of a factor of about 3.

Artifacts↗
PubMed1999

Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness.

OBJECTIVE: Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state. METHOD: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [15O]water and [18F]fluorodeoxyglucose, respectively. RESULTS: With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen--limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions. CONCLUSIONS: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression.

Affect↗
PubMed1999

Restricted expression of the zebrafish hsp90alpha gene in slow and fast muscle fiber lineages.

Members of the heat shock protein 90 (Hsp90) family of molecular chaperones play important roles in allowing a select group of intracellular signaling molecules reach and maintain functionally active conformations. We have previously shown that hsp90alpha gene expression in early zebrafish embryos is restricted to a subgroup of paraxial-mesoderm derived somitic cells prior to muscle formation and that the gene is downregulated in mature trunk and tail muscle fibers. Here we have compared the expression of the hsp90alpha gene to muscle regulatory genes during development of slow and fast muscle fibers in normal embryos and in embryos carrying mutations which affect somitic muscle formation. We show that hsp90alpha is first expressed early during the development of slow somitic muscle progenitors shortly following myoD activation and at a point prior to or co-incident with the expression of other known muscle regulatory genes. Expression of hsp90alpha is also activated in the midline of flh mutants when these cells switch from a notochord to a muscle fate. Conversely, expression is not detectable in cells of the paraxial mesoderm lineage which fail to converge in spt mutants and which do not activate expression of other muscle specific marker genes. Finally, expression of hsp90alpha is downregulated in slow muscle fibers by 24 h of age but becomes detectable in the later developing fast fibers at this time. Thus, hsp90alpha is expressed in developing muscle progenitors during short temporal and spatial windows of both slow and fast fiber lineages in the zebrafish somite.

Animals↗
PubMed1998

Social functioning and facial emotional expression in neurological and psychiatric disorders.

This study examined the relationship between facial expression and social functioning in schizophrenic, depressed, right-brain-damaged, Parkinson's disease, and normal adult participants. Raters evaluated general intensity and amount of positive and negative facial emotion while participants were producing monologues regarding pleasant and unpleasant experiences. Social functioning items were derived from three standardized inventories. Overall, patient groups displayed more negative and less positive emotion than normals, and the schizophrenic and right-brain-damaged groups showed less intense expressions than normals. Correlational analyses suggested that the more intense the facial expressions, the better the social functioning, and that the more negative emotion displayed, the poorer the social functioning.

Journal Article↗
PubMed1997

Cingulate function in depression: a potential predictor of treatment response.

The relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed.

Adult↗
PubMed1997

Specific craniofacial cartilage dysmorphogenesis coincides with a loss of dlx gene expression in retinoic acid-treated zebrafish embryos.

Treatments of zebrafish embryos with retinoic acid (RA), a substance known to cause abnormal craniofacial cartilage development in other vertebrates, result in dose- and stage-dependent losses of dlx homeobox gene expression in several regions of the embryo. Dlx expression in neural crest cells migrating from the hindbrain and in the visceral arch primordia is particularly sensitive to RA treatment. The strongest effects are observed when RA is administered prior to or during crest cell migration but effects can also be observed if RA is applied when the cells have entered the primordia of the arches. Losses of dlx expression correlate either with the loss of cartilage elements originating from hindbrain neural crest cells or with abnormal morphology of these elements. Cartilage elements that originate from midbrain neural crest cells, which do not express dlx genes, are less affected. Taken together with the observation that the normal patterns of visceral arch dlx expression just prior to cartilage condensation resemble the morphology of the cartilage elements that are about to differentiate, our results suggest that dlx genes are an important part of a multi-step process in the development of a subset of craniofacial cartilage elements.

Animals↗