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At least 739 records · Page 41Linked to original sources
PubMed1992

Sensitivity of neurons in cat primary auditory cortex to tones and frequency-modulated stimuli. II: Organization of response properties along the 'isofrequency' dimension.

The spatial distribution of neuronal responses to tones and frequency-modulated (FM) stimuli was mapped along the 'isofrequency' dimension of the primary auditory cortex (AI) of barbiturate-anesthetized cats. In each cat, electrode penetrations roughly orthogonal to the cortical surface were closely spaced (average separation approximately 130 microns) along the dorsoventral extent of a single 'isofrequency' strip in high frequency parts of AI (> 15 kHz). Characteristic frequency (CF), minimum threshold, sharpness of frequency tuning (Q10 and Q20), the dynamic range of the spike count-intensity function at CF, sensitivity to the rate of change of frequency (RCF) and to the direction of frequency-modulation (DS) were determined for contralaterally-presented tone and FM stimuli. Sharpness of tuning attained maximum values at central loci along the dorsoventral 'isofrequency' axis and values declined towards more dorsal and more ventral locations. Minimum threshold and dynamic range varied between high and low values in a similar and correlated periodic fashion. Their combined organization yielded an orderly spatial representation of response strength, relative to maximum, as a function of stimulus amplitude. The distributions of the most common forms of FM rate sensitivity (RCF response categories) and best RCF along 'isofrequency' strips were significantly non-random although there was a considerable degree of variability between cats. FM directional preference and sensitivity appeared to be randomly distributed. Sharpness of tuning may be related to the analysis of the spectral content of an acoustic stimulus, both minimum threshold and dynamic range are related to the encoding of stimulus intensity, and measures of FM rate and directional sensitivity assess the coding of temporal changes of stimulus spectra. The independent, or for minimum threshold and dynamic range dependent, topographic organizations of these neuronal parameters therefore suggest parallel and independent processing of these aspects of acoustic signals in AI.

Acoustic Stimulation↗
PubMed2002

[The roles of DNA methylation in human neoplasms].

Recent data suggested that cancer appears to be a process that is fuelled both by genetic alterations and by epigenetic mechanisms. Epigenetics refer to the study of changes in gene expression that can be mitotically inherited, but is not associated with the changes in the coding sequence of the affected genes. DNA methylation, the best understood mechanism in epigenetics, is an enzyme-mediated chemical modification that adds methyl (CH3) groups at selected sites on DNA. In humans and most mammals, DNA methylation only affects the cytosine base (C), when it is followed by a guanosine (G). DNA methylation in the promoter regions is a powerful mechanism for the suppression of gene activity. It was thought formerly that two pathways by which tumor suppressor genes became disabled were intragenic mutations and loss of chromosomal material [(loss of heterozygosity (LOH) or homozygous deletion)]. More recent studies have firmly established methylation as one potential hit and represent a third mechanism by which tumor suppressor genes are inactivated, and that, in some cases, methylation is the sole mechanism responsible for the inactivation of a tumor suppressor gene. There is clearly a tumor-specific methylation pattern in many types of tumor. An individual tumor within a single patient may have characteristic set of gene with an increased propensity to become methylated as compared with a tumor of the same type in a different patient. Methylation changes appear to precede apparent malignancy in many cases. Therefore, methylation can distinguish tumor types and subtypes, and should be useful in improving early detection of potentially cancerous cells. Methylation markers may also be used to predict response to chemotherapy or duration of patient survival. The efficacy of hypomethylating agents (e.g. 5-aza-2'-deoxycytidine) as antineoplastic agents has been attributed to two distinct mechanism: cytotoxicity and induction of hypomethylation. Some clinical trials with them have been performed in solid tumors and malignant hematologic disease. In general, the response rates were not satisfactory. A variety of methods are used to evaluate the methylation status of genes. MSP (methylation-specific PCR) is very sensitive and has been widely used. It takes advantage of the DNA sequence difference existing between methylated and unmethylated DNA after bisulfite treatment.

CpG Islands↗
PubMed1985

Changes in the levels of three different classes of histone mRNA during murine erythroleukemia cell differentiation.

We used a gene-specific S1 nuclease assay to study the changes in steady-state mRNA levels of several core histone variants during the differentiation of murine erythroleukemia cells. These studies allowed us to distinguish three distinct expression classes of histone genes. The expression of the major replication-dependent class of histone genes was tightly linked to DNA synthesis. The concentrations of these transcripts decreased rapidly as cell division slowed during the process of differentiation. In contrast, the replication-independent H3.3 transcript levels were constitutively maintained throughout differentiation and were unaffected by inhibitors of DNA or protein synthesis. We also identified among the cloned histone genes used as probes a third expression class, the partially replication-dependent variants. Expression of these transcripts became transiently uncoupled from the reduced rate of DNA synthesis accompanying the early stages of differentiation. We show that their synthesis is sensitive to the DNA synthesis inhibitor hydroxyurea but that selective uncoupling from DNA synthesis of these histone mRNAs occurs at a specific stage of differentiation. We present several hypotheses to explain how this might be accomplished. The expression characteristics of the mRNAs studied coincided with those of the proteins for which they code, indicating that changes in the relative levels of the different variants is mediated at least in part by changes in mRNA levels.

Animals↗
PubMed1985

Molecular cloning and nucleotide sequences of cDNAs specific for rat liver ribosomal proteins S17 and L30.

cDNA clones coding for rat liver ribosomal proteins S17 and L30 have been isolated by positive hybridization-translation assay from a cDNA library prepared from 8-9S poly(A)+RNA from free polysomes of regenerating rat liver. The cDNA clone specific for S17 protein (pRS17-2) has a 466-bp insert with the poly(A) tail. The complete amino acid (aa) sequence of S17 protein was deduced from the nucleotide sequence of the cDNA. S17 protein consists of 134 aa residues with an Mr of 15 377. The N-terminal aa sequence of S17 protein determined by automatic Edman degradation is consistent with the sequence data. The aa sequence of S17 shows strong homology (76.9%) to that of yeast ribosomal protein 51 [Teem and Rosbash, Proc. Natl. Acad. Sci. USA 80 (1983) 4403-4407] in the two-thirds N-terminal region. The cDNA clone specific for L30 protein (pRL30) has a 394-bp insert. The aa sequence of L30 protein was deduced from the nucleotide sequence of the cDNA. The protein consists of 114 aa residues with an Mr of 12 652. When compared with the N-terminal aa sequence of rat liver L30 protein [Wool, Annu. Rev. Biochem. 48 (1979) 719-754], pRL30 was found not to contain the initiation codon and 5'-noncoding region. The cDNA showed twelve silent changes in the coding region, one point mutation and one base deletion in the 3'-noncoding region, compared with mouse genomic DNA for L30 protein [Wiedemann and Perry, Mol. Cell Biol. 4 (1984) 2518-2528].

Amino Acid Sequence↗
PubMed1991

[Experiences with color-coded duplex sonography in the diagnosis of extracranial vascular changes].

72 Patients with occurred transitory ischemie attacks and passed reversible neurologie deficits were duplexsonographically diagnosed. After wards a renewed duplexsonographic investigation with color coding followed in all patients. The patients were angiographically diagnosed within two weeks. As a result in three of ten patients with an unobtrusive angiogramm plaques formations were proved by means of the color codes duplexsonography.

Adult↗
PubMed2004

Long-term excretion of vaccine-derived poliovirus by a healthy child.

A child was found to be excreting type 1 vaccine-derived poliovirus (VDPV) with a 1.1% sequence drift from Sabin type 1 vaccine strain in the VP1 coding region 6 months after he was immunized with oral live polio vaccine. Seventeen type 1 poliovirus isolates were recovered from stools taken from this child during the following 4 months. Contrary to expectation, the child was not deficient in humoral immunity and showed high levels of serum neutralization against poliovirus. Selected virus isolates were characterized in terms of their antigenic properties, virulence in transgenic mice, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 1 strain. The VDPV isolates showed mutations at key nucleotide positions that correlated with the observed reversion to biological properties typical of wild polioviruses. A number of capsid mutations mapped at known antigenic sites leading to changes in the viral antigenic structure. Estimates of sequence evolution based on the accumulation of nucleotide changes in the VP1 coding region detected a "defective" molecular clock running at an apparent faster speed of 2.05% nucleotide changes per year versus 1% shown in previous studies. Remarkably, when compared to several type 1 VDPV strains of different origins, isolates from this child showed a much higher proportion of nonsynonymous versus synonymous nucleotide changes in the capsid coding region. This anomaly could explain the high VP1 sequence drift found and the ability of these virus strains to replicate in the gut for a longer period than expected.

Animals↗
PubMed2002

An algorithm for detecting directional and non-directional positive selection, neutrality and negative selection in protein coding DNA sequences.

Positive selection or adaptive evolution is thought to be responsible, at least some of the time, for the rapid accumulation of advantageous changes in protein-coding genes. The origin of new enzymatic functions, erection of barriers to heterospecific fertilization, and evasion of host response by pathogens, among other things, are thought to be instances of adaptive evolution. Detecting positive selection in protein-coding genes is fraught with difficulties. Saturation for sequence change, codon usage bias, ephemeral selection events and differential selective pressures on amino acids all contribute to the problem. A number of solutions have been proposed with varying degrees of success, however they suffer from limitations of not being accurate enough or being prohibitively computationally intensive. We have developed a character-based method of identifying lineages that undergo positive selection. In our method we assess the possibility that for each internal branch of a phylogenetic tree an event occurred that subsequently gave rise to a greater number of replacement substitutions than might be expected. We classify these replacement substitutions into two categories - whether they subsequently became invariable or changed again in at least one descendent lineage. The former situation indicates that the new character state is under strong selection to preserve its new identity (directional selection), while the latter situation indicates that there is a persistent pressure to change identity (non-directional selection). The method is fast and accurate, easy to implement, sensitive to short-lived selection events and robust with respect to sampling density and proportion of sites under the influence of positive selection.

Algorithms↗
PubMed1999

Human delta-opioid receptor gene and susceptibility to heroin and alcohol dependence.

In the present study, we tested the hypothesis that addictive behavior may be influenced by genetic variation in the human delta-opioid receptor gene. We investigated the contribution of a silent T to C change in the coding region to the development of heroin and alcohol dependence using large case-control and family-based association samples. Presence of the C allele was previously reported to significantly increase the risk for heroin dependence. In the present study, however, we did not find statistically significant differences between patients and controls nor did we find preferential transmission of the C allele from parents to affected offspring. Our results, therefore, do not support an association between genetic variation of the delta-opioid receptor and addictive behavior in man.

Adult↗
PubMed1997

Fourteen novel mucopolysaccharidosis IVA producing mutations in GALNS gene.

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency of the lysosomal N-acetylgalactosamine-6-sulfate sulfatase. Here, we report our analysis of data on 21 patients of diverse ethnic and geographic origins studied by SSCP and sequencing analysis. Sixteen mutations were detected, including 14 new mutations (11 missense, one premature termination, one splice site alteration, and one cryptic site alteration). The donor splice site mutation (IVS4 + 1G-->A) predicts that normal splicing will be abolished and that translation would lead to an immediate premature termination (W141X). Another novel nucleotide change outside the coding sequence is an intronic alteration (IVS9-42C-->T:ggtcggtgcggttggtgc) creating a potential cryptic donor site. The nucleotide sequence surrounding this alteration is highly suggestive of a consensus donor splice site. All 12 missense and nonsense mutations were shown by transient expression to abolish or greatly reduce GALNS activity, thereby providing an explanation as to why they produce MPS IVA. All mutations were readily confirmed by restriction enzyme or by allelic specific oligonucleotide analysis (ASO). These findings, coupled with previously reported mutations, bring the total of different mutations to 41 among independent families with MPS IVA, illustrating the extensive allelic heterogeneity among mutations producing MPS IVA.

Chondroitinsulfatases↗
PubMed1990

Increasing incidence of primary gastric lymphoma.

Both the incidence and mortality rates of gastric cancer have been consistently declining over the past several decades in the United States. In contrast, the incidence of gastric lymphoma may have been increasing during this time. Based on data from the Surveillance, Epidemiology and End Results (SEER) Program, annual incidence rates of gastric lymphoma from 1973 to 1986 were examined. There was a twofold increase in the age-adjusted incidence rates of gastric lymphoma during this time. This increase occurred in both men and women but was limited to people over 60 years of age. Although the reasons for this increase are unknown, the authors speculate that this may be a true increase since neither differences in SEER coding practices nor changes in diagnostic procedures could explain these observations.

Abdomen↗
PubMed1998

Transgene-promoted epigenetic switches of chalcone synthase activity in petunia plants.

Epigenetic variation affecting pigment pattern formation in petunia flowers due to the insertion of transgenes encoding chalcone synthase is described. The loss of pigment formation in petals or parts of petals is due to the post-transcriptional degradation of chalcone synthase RNA, from both the endogenous petunia chalcone synthase genes and from the chalcone synthase transgenes. The RNA cleavage pathway and its control are described. Different epigenetic states of RNA breakdown are correlated with specific cytosine methylation changes in the coding sequences of the genes. The probability, extent and developmental location of chalcone synthase RNA breakdown are related to the number and organization of transgenes in the genome but epigenetic switches that affect RNA turnover probably occur in meristems and between sexual generations. Hypotheses to explain how the transgenes influence the levels of chalcone synthase RNA breakdown and how different epigenetic states are created are discussed.

Acyltransferases↗
PubMed2007

An investigation of the neurotrophic factor genes GDNF, NGF, and NT3 in susceptibility to ADHD.

Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable, neurodevelopmental disorder with onset in early childhood. Genes involved in neuronal development and growth are, thus, important etiological candidates and neurotrophic factors have been hypothesized to play a role in the pathogenesis of ADHD. Glial derived neurotrophic factor (GDNF), nerve growth factor (NGF (beta subunit)), and neurotrophic factor 3 (NT3) are members of the neurotrophin family and are involved in the survival, differentiation, and maintenance of neuronal cells. We have examined 10 coding and intronic single nucleotide polymorphisms (SNPs) across GDNF, NGF, and NT3 in a family-based association sample of 120 DSM-IV ADHD probands and their biological parents, as well as a case-control analysis with 120 sex-matched controls. Borderline significant overtransmission of the C allele of a non-synonymous C/T SNP (rs6330) in NGF which codes an alanine/valine change was found in the family-based sample (Chi-square = 3.69, odds ratio (OR) = 1.65, P = 0.05). Although this SNP is located in the 5' pro-NGF sequence and not the mature NGF protein, it may affect intracellular processing and secretion of NGF.

Adolescent↗
PubMed1998

Association between the gene encoding the E2 subunit of the alpha-ketoglutarate dehydrogenase complex and Parkinson's disease.

Dihydrolipoamide succinyltransferase (E2, EC 2.3.1.61, chromosome 14q24.2-3) is a specific subunit of human alpha-ketoglutarate dehydrogenase complex (KGDHC). A biallelic intragenic polymorphism was identified in E2 gene of KGDHC. It was a single nucleotide substitution between G (in allele 1) and A (in allele 2) at the position that does not change amino acid code. Using this intragenic polymorphism as a marker, we investigated the association between this gene and Parkinson's disease. Frequencies of the genotypes that carry allele 2 were significantly higher in the Parkinson's disease group than in the control group. The results indicated that a genetic variant of the E2 gene itself or in close proximity to the gene constitutes one of the genetic risk factors for Parkinson's disease.

Age Distribution↗
PubMed2005

Distribution and fate of cocaine- and amphetamine-regulated transcript peptide (CARTp)-expressing cells in rat urinary bladder: a developmental study.

We examined the distribution and fate of cocaine- and amphetamine-regulated transcript peptide (CARTp)(55-102)-immunoreactive (IR) structures in the neonatal and adult rat urinary bladder. Double-labeling studies examining CARTp with tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), or choline acetyltransferase (ChAT) were performed in wholemounts of urothelium or detrusor or cryostat sections of the bladder. In younger animals (postnatal day [P]1, P3), CARTp-IR cell bodies in detrusor smooth muscle were observed in large clusters ( approximately 100 cells/cluster) at the ureteral insertion and along thick bundles of nerve fibers at the bladder base. The total number of CARTp-IR cells was significantly reduced (by five-fold) at P14, and this reduced number persisted into adulthood. The decrease in the number of CARTp-expressing cells was complemented with positive staining for cleaved caspase-3, suggesting that apoptosis contributed to this decrease. At birth (P1), all CARTp-IR cells expressed the neuronal marker Hu. After birth, CARTp was expressed by some neurons (CARTp-IR, Hu-IR) that represent intramural ganglion cells and by cells that lacked a neuronal phenotype (CARTp-IR, Hu-) but did express TH. Neither of these cell populations expressed ChAT immunoreactivity in adult bladder. These cells (CARTp-IR, Hu-, TH-IR) may represent paraganglion or small intensely fluorescent (SIF) cells. The percentage of colocalization of CARTp-IR and nNOS or TH was dependent on postnatal age and showed an inverse relationship. At P1, 67.1 % of CARTp-IR cells expressed nNOS immunoreactivity. Decreased colocalization was observed with increasing postnatal age. In contrast, 19.5% of CARTp-IR cells expressed TH at P1, but colocalization increased with postnatal age. The suburothelial plexus lacked CARTp-IR nerve fibers until P14, when nerve fibers with varicosities were observed in the urethra and bladder neck region. In summary, we demonstrate 1) a decrease in the number of CARTp-IR cells in rat detrusor in early postnatal development; 2) apoptotic events in the bladder during early postnatal development; 3) rostral migration of CARTp-IR cells from the ureteral insertion toward the bladder body during postnatal development; 4) the presence of different populations of CARTp-IR cells, some with and others without a neuronal phenotype; and (5) age-dependent changes in chemical coding of CARTp-IR cells with postnatal development. This study demonstrates that CARTp-IR intramural ganglia and CARTp-IR paraganglion or SIF cells exist in the postnatal and adult rat bladder, although the role of these cell types remains to be determined.

Aging↗
PubMed1994

Polymerase chain reaction-directed DNA sequencing of bleomycin-induced "nondeletion"-type, 6-thioguanine-resistant mutants in Chinese hamster ovary cell derivative AS52: effects of an inhibitor and a mimic of superoxide dismutase.

Bleomycin-induced, 6-thioguanine-resistant, "non deletion" mutants pretreated with or without either TRIEN (triethylenetetramine), a superoxide dismutase (SOD) inhibitor, or TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a SOD mimic, were analyzed by polymerase chain reaction (PCR)-directed DNA sequencing in a Chinese hamster ovary (CHO) cell derivative, AS52. Among the 23 bleomycin-induced mutants, six have 3-bp 5'-TGA-3' deletions in the region of 366-371, five have single-base deletions, seven have base substitutions, three have insertions, and two have possible translocations. Among the 16 bleomycin-induced mutants pretreated with TRIEN, six have the 5'-TGA-3' deletion (366-371), two have single-base deletions, one has a 13-bp deletion, four have single-base substitutions, one has a double-base substitution, and two have insertions. Among the 17 bleomycin-induced mutants pretreated with TEMPOL, six have the same TGA deletions, two have single-base deletions, two have single-base insertions, four have single-base substitutions, one mutant has a 12-bp deletion, one has a 13-bp deletion, and one mutant shows no detectable change in its coding region in the DNA sequence. A possible shift from a ROS-mediated mutational spectrum to a spontaneous mutational spectrum by TRIEN further indicates that reactive oxygen species play an important role in bleomycin mutagenesis in mammalian cells.

Animals↗
PubMed2004

Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer.

Mutations in the base excision repair gene MYH have recently been shown to confer recessive susceptibility to colorectal adenomas and carcinomas. To evaluate the contribution of germline MYH mutations to early-onset colorectal cancer, we screened a series of 358 unselected early-onset cases for germline changes in the coding sequence of the gene. Two cases harbored biallelic germline mutations (0.6%; 95% CI = 0.06-2.0) and 8 single MYH mutations (2.2%; 95% CI = 0.9-4.4). Both cases harboring biallelic MYH mutations had multiple polyps but not profuse polyposis. All cases had distally sited tumors. No biallelic mutations were detected among 354 controls. These results confirm that biallelic MYH mutations confer susceptibility to colorectal cancer but are unlikely to account for more than 3% of early-onset colorectal cancer.

Adenocarcinoma↗
PubMed1984

A site-specific mutation within the active site of ribulose-1,5-bisphosphate carboxylase of Rhodospirillum rubrum.

In vitro mutagenic techniques have generated an asp-->glu substitution at residue 198 adjacent to the carbamate-divalent metal ion binding site of Rhodospirillum rubrum ribulose 1,5-bisphosphate carboxylase. A single C-->A nucleotide change in the coding strand created the mutant and introduced a new EcoRI restriction site on the expression plasmid pRR2119. Although the carboxylase:oxygenase ratio remained the same, the mutant enzyme had slightly altered kinetic properties. The e.p.r. spectra of the quaternary complexes enzyme.activator carbamate.Mn.2-carboxyarabinitol 1,5-bisphosphate and enzyme.activator carbamate.Mn.4-carboxyarabinitol 1,5-bisphosphate for mutant and wild-type enzymes were different, indicating that the metal ion was in a slightly altered environment. These findings are consistent with the hypothesis that, besides the carbamate at lys 201, the carboxyl group of asp 198 contributes to the formation of the divalent metal ion binding site.

Journal Article↗
PubMed1987

Structure and expression of the mouse myelin proteolipid protein gene.

The gene for the mouse myelin proteolipid protein has been isolated and the seven exons have been sequenced. Since the sequence of a rat proteolipid protein cDNA and partial sequence of the human proteolipid protein gene have been determined, it was possible to demonstrate a very high degree of conservation for the proteolipid protein gene exons among species. While there are some nucleotide changes, the protein coding region of the mouse gene encodes protein that is totally conserved relative to both rat and human proteolipid proteins. The regulatory and noncoding regions of the proteolipid protein gene are also highly conserved. The upstream regulatory and 5'-noncoding region of the gene is 92% homologous to the comparable region of the human proteolipid protein gene, and the 3'-noncoding region of the mouse gene is approximately 90% homologous to a rat proteolipid protein cDNA through 2,200 nucleotides of 3'-noncoding DNA. S1 nuclease protection experiments indicated that the major 5'-end for proteolipid protein mRNAs from mouse, rat, human, or baboon is approximately 147-160 nucleotides upstream from the initial methionine codon of the protein coding region. Other S1 nuclease protection experiments indicated the possible existence of an alternative splice site within exon 3, which may produce mRNA for DM20. This mRNA is approximately 100 nucleotides shorter than that for the proteolipid protein, and it is missing the latter half of exon 3, that is, amino acids 116-150 of the proteolipid protein sequence.

Amino Acid Sequence↗