Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “repeat interruptions”

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

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

At least 847 records · Page 47Linked to original sources
PubMed2005

On the structural differences between markers and genomic AC microsatellites.

AC microsatellites have proved particularly useful as genetic markers. For some purposes, such as in population biology, the inferences drawn depend on the quantitative values of their mutation rates. This, together with intrinsic biological interest, has led to widespread study of microsatellite mutational mechanisms. Now, however, inconsistencies are appearing in the results of marker-based versus non-marker-based studies of mutational mechanisms. The reasons for this have not been investigated, but one possibility, pursued here, is that the differences result from structural differences between markers and genomic microsatellites. Here we report a comparison between the CEPH AC marker microsatellites and the global population of AC microsatellites in the human genome. AC marker microsatellites are longer than the global average. Controlling for length, marker microsatellites contain on average fewer interruptions, and have longer segments, than their genomic counterparts. Related to this, marker microsatellites show a greater tendency to concentrate the majority of their repeats into one segment. These differences plausibly result from scientists selecting markers for their high polymorphism. In addition to the structural differences, there are differences in the base composition of flanking sequences, marker flanking regions being richer in C and G and poorer in A and T. Our results indicate that there are profound differences between marker and genomic microsatellites that almost certainly affect their mutation rates. There is a need for a unified model of mutational mechanisms that accounts for both marker-derived and genomic observations. A suggestion is made as to how this might be done.

Base Composition↗
PubMed1995

Organization of the gene encoding cellular nucleic acid-binding protein.

The human cellular CNBP gene locus has been sequenced and is comprised of 6453 bp from the transcription start point (tsp) to the polyadenylation signal, and an additional 201 bp of 5' and 259 bp of 3' flanking sequences. The gene consists of five exons, four of which contain coding information for two alternatively spliced products, CNPB alpha and beta. The open reading frame (ORF) of 177 amino acids (aa) is encoded by exons 2 through 4 (CNBP alpha, M(r) 19463). The protein contains seven zinc-finger (Zf) domains. CNBP beta lacks seven aa in the linker region between the first two Zf, because of the use of an alternative 5' donor site within exon 2. The sixth Zf is the only Zf domain that is not completely encoded within a single exon and is interrupted by an intron (intron 4). The 5' untranslated region (UTR) contains 849 bp and is interrupted by intron 1. The 3' UTR, ending at the polyadenylation signal, is 857 bp long and is contained within exon 5. One Alu repeat was identified within intron 1, the largest intron of CNBP.

Amino Acid Sequence↗
PubMed2004

Changes in P300 amplitude during an active standard auditory oddball task.

This study evaluated whether P300 amplitude declines in response to repeated presentation of the target in a standard auditory oddball task; to what extent the decrease is affected by the number of targets presented, interrupted by an interblock interval (IBI, 3 min) and consistent. We also aimed to identify factors inducing P300 amplitude decrease and its psychological significance. Two blocks of 500 tones (each divided into five subblocks of 100 tones) were presented. First block: P300 amplitude was smaller in the first subblock than in the second, which we attribute to processing resources during the first subblock being divided between the task of identifying the target and the process of estimating subjective probability. Amplitude decreased from the second subblock onwards. The interblock interval was sufficient for amplitude to return to pre-decrease levels. The intrablock decline was replicated in the second block. The decline in P300 amplitude might to reflect a progressive automation of the context-updating operations.

Adolescent↗
PubMed1999

Aberrant splicing of the Drosophila melanogaster phenylalanine hydroxylase pre-mRNA caused by the insertion of a B104/roo transposable element in the Henna locus.

We report the insertion of the transposable element B104 in the Phenylalanine hydroxylase gene of the Drosophila mutant Henna-recessive 3. Its presence alters the Phenylalanine hydroxylase splicing pattern, producing at least two aberrant mRNAs which contain part of the B104 sequence interrupting the coding region. This aberrant splicing is provoked by the use of a cryptic donor site encoded by the B104 3' long terminal repeat in combination with either the gene intron 3 acceptor site or a novel acceptor site generated by the target duplication caused by transposition. One of them, referred as mRNA type 1, encodes a truncated protein that could be predictably non-functional. In mRNA type 2, in spite of a 42 nt insertion, the Phenylalanine hydroxylase reading frame is not altered and it would encode for a protein with 14 extra amino acids which would be able to account for the low enzyme activity detected in this mutant. These results demonstrated that Henna locus encodes the enzyme phenylalanine hydroxylase providing direct evidence of its participation in pteridine synthesis. Moreover, it constitutes an example of the ability of transposable elements to generate protein variation in populations with the evolutionary consequences that this implies.

Alternative Splicing↗
PubMed2004

Retrotransposon-derived elements in the mammalian genome: a potential source of disease.

The plethora of genomic information gathered by the sequencing of the human and mouse genomes has paved the way for a new era of genetics. While in the past we focused mainly on the small percentage of DNA that codes for proteins, we can now concentrate on the remainder, i.e. the noncoding sequences that interrupt and separate genes. This portion of the genome is made up, in most part, of repetitive DNA sequences including DNA transposons, long terminal repeat (LTR) retrotransposons, LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements). Some of these elements are transcriptionally active and can transpose or retrotranspose around the genome, resulting in insertional mutagenesis that can cause disease. In these cases, insertions have occurred in the coding sequence. However, recent evidence suggests that the main effect of these elements is their ability to influence transcription of neighbouring genes. The elements themselves contain promoters that can initiate transcription of flanking genomic DNA. Furthermore, they are susceptible to epigenetic silencing, which is often stochastic and incomplete, resulting in complex patterns of transcription. This review discusses some diseases in both human and mouse that are caused by these repetitive elements.

Animals↗
PubMed1979

Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production.

Although gonadotropin-releasing hormone (GnRH) is believed to mediate the hypothalamic control of pituitary gonadotropin secretion, continuous or repeated administration of GnRH or its agonist analogues has been shown to cause paradoxical antifertility effects in several species, including primates. GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum. These luteolytic effects have been attributed to the well recognized desensitising actions of elevated luteinising hormone (LH) levels on ovarian LH receptors and steroidogenesis, subsequent to GnRH-induced gonadotropin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum progesterone levels during early pregnancy in rats, whereas a highly active GnRH analogue was effective in this regard. These observations suggested that GnRH and its agonist analogues, given in high or sustained doses, can exert a direct action on the ovary that is independent of the pituitary. This hypothesis was further supported by the ability of GnRH and its agonists to inhibit human chorionic gonadotropin (HCG)-induced ovarian and uterine weight gain in hypophysectomised rats and to delay the onset of puberty in intact female rats. Also, GnRH and its agonist analogues have recently been shown to inhibit steroidogenesis induced by follicle-stimulating hormone (FSH) in cultured granulosa cells, confirming the direct action of such peptides on the ovarian follicle. The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells. The present experiments, which examine the effects of GnRH agonists on luteal steroidogenesis, demonstrate the existence of such actions and their mediation by specific high-affinity receptor sites present in luteal cell membranes.

Animals↗
PubMed2007

Modern origin of numerous alternatively spliced human introns from tandem arrays.

Despite the widespread occurrence of spliceosomal introns in the genomes of higher eukaryotes, their origin remains controversial. One model proposes that the duplication of small genomic portions could have provided the boundaries for new introns. If this mechanism has occurred recently, the 5' and 3' boundaries of each resulting intron should display distinctive sequence similarity. Here, we report that the human genome contains an excess of introns with perfect matching sequences at boundaries. One-third of these introns interrupt the protein-coding sequences of known genes. Introns with the best-matching boundaries are invariably found in tandem arrays of direct repeats. Sequence analysis of the arrays indicates that many intron-breeding repeats have disseminated in several genes at different times during human evolution. A comparison with orthologous regions in mouse and chimpanzee suggests a young age for the human introns with the most-similar boundaries. Finally, we show that these human introns are alternatively spliced with exceptionally high frequency. Our study indicates that genomic duplication has been an important mode of intron gain in mammals. The alternative splicing of transcripts containing these intron-breeding repeats may provide the plasticity required for the rapid evolution of new human proteins.

Alternative Splicing↗
PubMed1977

Gene-sized DNA molecules of the Oxytricha macronucleus have the same terminal sequence.

The DNA in the macronucleus of the ciliated protozoan Oxytricha exists as small linear molecules with a number average size of about 3000 base pairs. Most, and possibly all, of these DNA molecules contain the same inverted terminal repeat sequence of approximately 26 base pairs. In addition to its terminal location, two inverted copies of this same sequence surround single-strand interruptions within these DNA molecules. This sequence arrangement may function in the processing of these molecules from large chromosomal precursors or in the subsequent replication of these small linear DNAs during cell reproduction.

Base Sequence↗
PubMed1998

Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection.

Trypanosoma cruzi is the causative agent of Chagas' disease. The major protease, cruzain, is a target for the development of new chemotherapy. We report the first successful treatment of an animal model of Chagas' disease with inhibitors designed to inactivate cruzain. Treatment with fluoromethyl ketone-derivatized pseudopeptides rescued mice from lethal infection. The optimal pseudopeptide scaffold was phenylalanine-homophenylalanine. To achieve cure of infection, this pseudopeptide scaffold was incorporated in a less toxic vinyl sulfone derivative. N-methyl piperazine-Phe-homoPhe-vinyl sulfone phenyl also rescued mice from a lethal infection. Six of the treated mice survived over nine months, three without further treatment. Three mice that had entered the chronic stage of infection were retreated with a 20-d regimen. At the conclusion of the experiments, five of the six mice had repeated negative hemacultures, indicative of parasitological cure. Studies of the effect of inhibitors on the intracellular amastigote form suggest that the life cycle is interrupted because of inhibitor arrest of normal autoproteolytic cruzain processing at the level of the Golgi complex. Parasites recovered from the hearts of treated mice showed the same abnormalities as those treated in vitro. No abnormalities were noted in the Golgi complex of host cells. This study provides proof of concept that cysteine protease inhibitors can be given at therapeutic doses to animals to selectively arrest a parasitic infection.

Amino Acid Chloromethyl Ketones↗
PubMed1981

Dialysis treatment in schizophrenia: two years experience.

The authors summarize two years trial of dialysis treatment of schizophrenia. Twenty-five schizophrenic patients were treated with hemodialysis using PAN membranes. The dialysis schedule was: dialyzer; RP 610; blood flow: 250 ml/min; dialysate flow: 500 ml/min; time: 3 hr; vascular access: arteriovenous fistula, femoral vein, antebrachial veins. Dialysis was first performed for three days, repeated after one week, two weeks, three weeks, and one month, and then performed once a month. The drug regimen was never modified or interrupted. The results were evaluated with the Overall and Lorr scale. Nine patients interrupted the treatment early and were not considered; nine patients showed disappearance of psychiatric symptomatology (Overall and Lorr index decreased to 21.8 at 2); non-significant modifications of the main schizophrenic symptoms were observed in seven patients. According to our trial, dialysis with polyacrylonitrile membranes can modify the psychotic attitude in a group of schizophrenic "dialysis responders".

Acrylic Resins↗
PubMed2000

Does status epilepticus influence the motor development of immature rats?

PURPOSE: To study the effect of severe status epilepticus (SE) on the motor development of rats. METHODS: SE was induced in 12-day-old rats (P12 group) and 25-day-old rats (P25 group) using the lithium-pilocarpine model. Seizures were interrupted after 2 hours by paraldehyde with an intraperitoneal dose of 0.3 or 0.6 mL/kg, respectively. Starting 3 days after SE, all animals were repeatedly exposed to a battery of motor and behavioral tests, including the bar-holding test, rotarod test, and open field test. RESULTS: In P12 animals, motor impairment occurred 2 months after SE, when significantly worse performance in the rotarod test was found. No difference between controls and experimental rats was found in any other test used. In contrast, P25 animals were significantly poorer in the bar-holding test from postnatal day 34 until adulthood. In open field study, P25 rats were found to be hyperactive during the whole period of testing, whereas P12 animals exhibited an initial period of hypoactivity (in the first test) that was replaced by hyperactivity that lasted until 2 months of age. In the last test performed at the age of 98 days, experimental P12 animals were again less active than age-matched controls. CONCLUSIONS: Animals of both age groups exhibited permanent changes of motor performance; however, both the pattern and the time course of these changes was related to age when SE was elicited.

Age Factors↗
PubMed1995

Characterization of the 23S and 5S rRNA genes of Coxiella burnetii and identification of an intervening sequence within the 23S rRNA gene.

Characterization of the rRNA operon from the obligate intracellular bacterium Coxiella burnetii has determined the order of the rRNA genes to be 16S-23S-5S. A 444-bp intervening sequence (IVS) was identified to interrupt the 23S rRNA gene beginning at position 1176. The IVS is predicted to form a stem-loop structure formed by flanking inverted repeats, and the absence of intact 23S rRNA molecules suggests that the loop is removed. An open reading frame in the IVS has been identified that shows 70% similarity at the amino acid level to IVS open reading frames characterized from four species of Leptospira.

Amino Acid Sequence↗
PubMed1989

Motion aftereffects with horizontally moving sound sources in the free field.

A horizontally moving sound was presented to an observer seated in the center of an anechoic chamber. The sound, either a 500-Hz low-pass noise or a 6300-Hz high-pass noise, repeatedly traversed a semicircular arc in the observer's front hemifield at ear level (distance: 1.5 m). At 10-sec intervals this adaptor was interrupted, and a 750-msec moving probe (a 500-Hz low-pass noise) was presented from a horizontal arc 1.6 m in front of the observer. During a run, the adaptor was presented at a constant velocity (-200 degrees to +200 degrees/sec), while probes with velocities varying from -10 degrees to +10 degrees/sec were presented in a random order. Observers judged the direction of motion (left or right) of each probe. As in the case of stimuli presented over headphones (Grantham & Wightman, 1979), an auditory motion aftereffect (MAE) occurred: subjects responded "left" to probes more often when the adaptor moved right than when it moved left. When the adaptor and probe were spectrally the same, the MAE was greater than when they were from different spectral regions; the magnitude of this difference depended on adaptor speed and was subject-dependent. It is proposed that there are two components underlying the auditory MAE: (1) a generalized bias to respond that probes move in the direction opposite to that of the adaptor, independent of their spectra; and (2) a loss of sensitivity to the velocity of moving sounds after prolonged exposure to moving sounds having the same spectral content.

Acceleration↗
PubMedDate not supplied

[Use of vecuronium and atracurium in continuous infusion. A comparative study using electromyography and accelerometry].

Vecuronium and atracurium, muscle relaxant agents of intermediate action, were administered in continuous infusion to 175 patients undergoing prolonged surgical operations with the purpose of achieving serum concentrations inducing maintained blocking of neuromuscular function. We used a 0.08 mg/kg or 0.5 mg/kg bolus intubation dose followed by a continuous infusion of vecuronium (72 patients) or atracurium (103 patients) 10 minutes after, at the necessary pace to maintain inhibition of neuromuscular transmission over 90%. Monitoring of relaxation was done by means of four supramaximal stimuli trains which were repeated every 20 seconds and applied to the cubital nerve. Composite electromyogram (electromyography) and thumb acceleration (mechanomyography-accelerometry) were simultaneously recorded. Infusion was interrupted 15 minutes before ending the operation; reversion occurred spontaneously in 143 patients and 32 patients had to be reversed with neostigmine. Beginning of action, total duration of infusion, infusion speed, and 25-75 spontaneous and after decurarization recovery index were measured. Initial dose allowed an easy tracheal intubation and the constant relaxation achieved with 0.068 mg/kg/h and 0.46 mg/kg/h infusion of vecuronium and atracurium was adequate for all operations. Spontaneous recovery is often adequate at the end of operations in carefully monitored patients. Both monitoring methods are useful for clinical evaluation of neuromuscular transmission.

Adolescent↗
PubMedDate not supplied

False uroradiologic pathology in children with urinary tract infection and fecal impaction.

Intravenous pyelography (IVP) in 5 children with urinary tract infection detected various uroradiologic abnormalities. Despite the lack of history of constipation, a common denominator to all 5 patients was the finding of fecal impaction in the rectosigmoid. In the first 3 patients, repeated complete IVP series done several weeks later and after preparatory bowel enema were normal. In the last 2 patients, the radiologic investigation was interrupted when the first exposure disclosed uroradiologic abnormalities and fecal impaction. Following immediate bowel enema, the studies were completed on the same settings to be found normal. It is concluded that in the face of fecal impaction, pathologic uroradiologic findings should be interpreted with great caution. Moreover, in such cases, intraprocedure cleansing enema is feasible and recommended.

Adolescent↗
PubMed1982

Structural organization of the corticotropin-beta-lipotropin precursor gene.

The human and the bovine corticotropin (ACTH)-beta-lipotropin (LPH) precursor gene have been isolated and characterized. Both genes consist of three exons which are divided by two large introns at exactly the same positions. One of the introns is inserted within the segment transcribed into the 5'-untranslated region of the mRNA, and the other interrupts the protein-coding sequence near the signal peptide region. The largest exon encodes most of the protein sequence which includes the three repeated melanotropin (MSH) peptides and other biologically active peptides such as ACTH and beta-endorphin. Thus, there is no apparent correspondence between the repetitive structure of the precursor protein and the structural organization of its gene. Comparison of the nucleotide sequences of the human and the bovine gene reveals that three regions are highly conserved, i.e., the region extending from the signal peptide to gamma-MSH, the ACTH region and the beta-MSH/beta-endorphin region. This suggests that the peptide(s) in the amino-terminal region, including gamma-MSH, may be of physiological importance, as is the case for ACTH and beta-endorphin. The different biologically active component peptides of the ACTH-beta-LPH precursor, encoded by a single gene, seem to be involved in the defense mechanism of the living organism by acting coordinately in the central nervous system as well as in peripheral tissues. The identification of the mRNA encoding the ACTH-beta-LPH precursor in a human ectopic ACTH-producing tumor is also reported.

Adrenocorticotropic Hormone↗
PubMed2006

Conformational features of a natural break in the type IV collagen Gly-X-Y repeat.

Fibrillar collagens have an absolute requirement for Gly as every 3rd residue, whereas breaks in the Gly-X-Y repeating pattern are found normally in the triple helix domains of non-fibrillar collagens, such as type IV collagen in basement membranes. In this study, a model 30-mer peptide is designed to include the interruption GPOGAAVMGPOGPO found in the alpha5 chain of type IV collagen. The GAAVM peptide forms a stable triple helix, with Tm= 29 degrees C. When compared with a control peptide with Gly as every 3rd residue, the GAAVM peptide has a marked decrease in the 225 nm maximum of its CD spectrum and a 10 degrees C drop in stability. A 50% decrease in calorimetric enthalpy is observed, which may result from disruption of ordered water structure anchored by regularly placed backbone carbonyls. NMR studies on specific 15N-labeled residues within the GAAVM peptide indicate a normal triple helical structure for Gly-Pro-Hyp residues flanking the break. The sequence within the break is not disordered but shows altered hydrogen exchange rates and an abnormal Val chemical shift. It was previously reported that a peptide designed to model a similar kind of interruption in the peptide (Pro-Hyp-Gly)10, (GPOGPOPOGPO), is unable to form a stable triple helix, and replacement of GAA by GPO or VM by PO within the GAAVM break decreases the stability. Thus, rigid imino acids are unfavorable within a break, despite their favorable stabilization of the triple helix itself. These results suggest some non-random structure typical of this category of breaks in the Gly-X-Y repeat of the triple helix.

Amino Acid Sequence↗
PubMed2003

Long-lasting delayed hyperalgesia after chronic restraint stress in rats-effect of morphine administration.

Different effects upon the nociceptive response have been observed with exposure to acute and chronic stress in rats. In the present study we repeatedly submitted rats to restraint for 40 days, inducing hyperalgesia using the tail-flick test. A new session of acute stress was applied at the end of 40 days period, and the chronically-stressed animals demonstrated analgesia after forced swimming, but not after restraint. The effect of stress interruption for 14 or 28 days on the nociceptive threshold was then investigated. The basal tail-flick latency remained decreased for at least 28 days (hyperalgesic effect). Following the periods of suspension, the animals were submitted to new session of acute restraint, and stress-induced analgesia was observed only after 28 days of stress interruption. Thus, the mechanisms involved in the long-lasting hyperalgesia presented in this study are not exactly the same as those responsible for the analgesia induced by acute stressors. After 40 days of chronic stress treatment, morphine was injected i.p. (1.0, 5.0 mg/kg or saline). The repeatedly stressed rats displayed decreased morphine effects on nociception compared to unstressed controls. The tolerance of the response to morphine agrees with previous studies suggesting that chronic restraint stress could modify the activity of opioid systems.

Animals↗