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At least 1,621 records · Page 90Linked to original sources
PubMed1999

Sequence specificity of in vivo reverse splicing of the Tetrahymena group I intron.

Reverse splicing of group I introns is proposed to be a mechanism by which intron sequences are transferred to new genes. Integration of the Tetrahymena intron into the Escherichia coli 23S rRNA via reverse splicing depends on base pairing between the guide sequence of the intron and the target site. To investigate the substrate specificity of reverse splicing, the wild-type and 18 mutant introns with different guide sequences were expressed in E. coli. Amplification of intron-rRNA junctions by RT-PCR revealed partial reverse splicing at 69 sites and complete integration at one novel site in the 23S rRNA. Reverse splicing was not observed at some potential target sites, whereas other regions of the 23S rRNA were more reactive than expected. The results indicate that the frequency of reverse splicing is modulated by the structure of the rRNA. The intron is spliced 10-fold less efficiently in E. coli from a novel integration site (U2074) in domain V of the 23S rRNA than from a site homologous to the natural splice junction of the Tetrahymena 26S rRNA, suggesting that the forward reaction is less favored at this site.

Animals↗
PubMed2005

Plant microRNAs and development.

MicroRNAs (miRNAs) act as negative regulators of gene expression in eukaryotes, a discovery that has opened an expanding field of biological research. Plant miRNAs are known to repress gene expression posttranscriptionally, mainly by guiding cleavage but also by attenuating the translation of target transcripts. In addition, it has been shown that plant miRNAs can also act at the transcriptional level by directing the methylation of target chromosomal loci. Genetic and biochemical approaches are quickly broadening our knowledge of the biogenesis and function of plant miRNAs. Computational approaches have uncovered an unexpectedly large number of miRNAs and their targets in plants. The targets of plant miRNAs often belong to families of transcription factors involved in the control of developmental processes. We review the status of research in this dynamic field, summarizing recent advances in our understanding of the biogenesis and mechanism of action of plant miRNAs, as well as in the developmental processes they regulate.

Base Sequence↗
PubMed2001

The Drosophila ribbon gene encodes a nuclear BTB domain protein that promotes epithelial migration and morphogenesis.

During development of the Drosophila tracheal (respiratory) system, the cell bodies and apical and basal surfaces of the tracheal epithelium normally move in concert as new branches bud and grow out to form tubes. We show that mutations in the Drosophila ribbon (rib) gene disrupt this coupling: the basal surface continues to extend towards its normal targets, but movement and morphogenesis of the tracheal cell bodies and apical surface is severely impaired, resulting in long basal membrane protrusions but little net movement or branch formation. rib mutant tracheal cells are still responsive to the Branchless fibroblast growth factor (FGF) that guides branch outgrowth, and they express apical membrane markers normally. This suggests that the defect lies either in transmission of the FGF signal from the basal surface to the rest of the cell or in the apical cell migration and tubulogenesis machinery. rib encodes a nuclear protein with a BTB/POZ domain and Pipsqueak DNA-binding motif. It is expressed in the developing tracheal system and other morphogenetically active epithelia, many of which are also affected in rib mutants. We propose that Rib is a key regulator of epithelial morphogenesis that promotes migration and morphogenesis of the tracheal cell bodies and apical surface and other morphogenetic movements.

Amino Acid Sequence↗
PubMed2001

Spatially restricted activity of a Drosophila lipid phosphatase guides migrating germ cells.

Temporal and spatial controls of cell migration are crucial during normal development and in disease. Our understanding, though, of the mechanisms that guide cells along a specific migratory path remains largely unclear. We have identified wunen 2 as a repellant for migrating primordial germ cells. We show that wunen 2 maps next to and acts redundantly with the previously characterized gene wunen, and that known wunen mutants affect both transcripts. Both genes encode Drosophila homologs of mammalian phosphatidic acid phosphatase. Our work demonstrates that the catalytic residues of Wunen 2 are necessary for its repellant effect and that it can affect germ cell survival. We propose that spatially restricted phospholipid hydrolysis creates a gradient of signal necessary and specific for the migration and survival of germ cells.

Acid Phosphatase↗
PubMed1996

[A case of tuberculous infection of emphysematous bulla in the superior segment of left lower lobe].

We report a case of tuberculous infection of emphysematous bulla, who is a 71-years-old male and ex-smoker. He had no past-history and had been treated for chronic obstructive pulmonary disease. At the periodical consultation on Sept 28 '95, abnormal shadow was found in left middle lung field on plain chest X-ray without any exacerbation of symptoms. Nearly alllaboratory tests on admission were within normal limit, except of slight elevation of inflammatory markers and slight hypoxemia. The Mantoux's skin test was positive. Roentogenologically, the air-fluid level was detected in the bulla of superior segment of left lower lobe. By percutaneous thoracentesis of the bulla under fluoloscopy and ultrasonic echo-guide, the fluid in the bulla was obtained. The fluid was exudate, the activities of ADA and LDH were elevated, but neutrophils were more dominant than lymphocytes in the fluid. The MTD test was positive, which amplifies rRNA of Mycobacterium tuberculosis (MTB), and MTB were cultered after four weeks from the fluid. However, MTB was not cultured from sputum and bronchial washing of left S6 via bronchoscope. After the administration of RFP, INH and EB, the fluid gradually disappeared with reduction of the size of bulla. We discussed the usefulness of the examination of the fluid in the bulla, especially the measurement of the activity of ADA and the MTD test for the confirmation of diagnosis as tuberculosis.

Adenosine Deaminase↗
PubMed2004

Par6alpha signaling controls glial-guided neuronal migration.

Neuronal migrations along glial fibers provide a primary pathway for the formation of cortical laminae. To examine the mechanisms underlying glial-guided migration, we analyzed the dynamics of cytoskeletal and signaling components in living neurons. Migration involves the coordinated two-stroke movement of a perinuclear tubulin 'cage' and the centrosome, with the centrosome moving forward before nuclear translocation. Overexpression of mPar6alpha disrupts the perinuclear tubulin cage, retargets PKCzeta and gamma-tubulin away from the centrosome, and inhibits centrosomal motion and neuronal migration. Thus, we propose that during neuronal migration the centrosome acts to coordinate cytoskeletal dynamics in response to mPar6alpha-mediated signaling.

Animals↗
PubMed1996

Intron-encoded, antisense small nucleolar RNAs: the characterization of nine novel species points to their direct role as guides for the 2'-O-ribose methylation of rRNAs.

A growing number of small nucleolar RNAs (snoRNAs) are intron-encoded, contain the characteristic box C (UGAUGA) and box D (CUGA) motifs and exhibit long complementarities to conserved sequences in mature rRNAs. We have identified nine additional members of this family, U32 to U40. All but one are encoded in introns of ribosomal protein genes in vertebrates: U32 to U35 in rpL13a, U36 in rpL7a and U38 to U40 in rpS8. By contrast, U37 is encoded in elongation factor 2 gene. Interestingly, U32 and U36 each contain two complementarities (one to 18 S and the other to 28 S rRNA). U32 to U40 are fibrillarin-associated, devoid of a 5'-trimethyl-cap and display an exclusively nucleolar localization. They are all metabolically stable and roughly as abundant as previously reported members of this family. Characterization of their homologs in distant species shows that their 10 to 14 nt long rRNA complementarities are conserved. A clue on the function of this snoRNA family is provided by the comparative analysis of the largely expanded collection of their conserved duplexes with rRNA. Not only does each duplex span at least one site of 2'-O-ribose methylation in the rRNA but the modification site is always at the same position in the duplex, paired to the fifth nucleotide upstream from a box D motif in the snoRNA. Consistent with the notion that each snoRNA of this family guides one particular methylation along the rRNA sequence, we have detected several pairs of snoRNAs with overlapping complementarities to rRNA tracts with vicinal sites of ribose methylations. In each case, the two overlapping complementarities are shifted from each other by a distance equal to the spacing between the methylated sites which are thus found at the same position within each of the mutually exclusive duplexes. Finally, we have also identified, within three previously known snoRNAs, novel antisense elements able to form a canonical duplex around ribose-methylated sites in rRNA, which further supports the conclusion that the duplex structure provides the 2'-O-methyltransferase with the appropriate site-specificity on the substrate.

Animals↗
PubMed1998

Clinician's guide to hepatitis C.

Hepatitis C virus infection is common, often silent, and almost always chronic and can lead to cirrhosis and hepatocellular cancer. Deaths related to chronic hepatitis C are expected to increase dramatically in the future. Many cases of infection are asymptomatic and are undiagnosed because of a lack of recognition by patients and physicians. All patients currently or previously at risk of infection should undergo screening, including those who received blood transfusions before 1992. Interferon is the only effective therapy, but disappearance of virus is sustained in only 10 to 15% of patients. The combination of interferon and oral ribavirin therapy may increase the sustained response rate to about 40%. New agents such as hepatitis C virus-specific protease inhibitors may be available in the next 5 to 10 years, and treatment is evolving toward multiple-drug regimens analogous to those used for human immunodeficiency virus (HIV) infection. In contrast to public funding for drug development in HIV, such funding for hepatitis C has been limited.

Biopsy↗
PubMed2000

Formation of a secondary corpus luteum after ultrasound-guided follicular aspiration in cows.

This paper reports the observed formation of a secondary corpus luteum (CL) in the presence of the cyclic corpus luteum, on the ovaries of a cow after ultrasound-guided follicular aspiration for oocyte recovery. The secondary structure, although smaller and lighter (4.97 g vs. 6.02 g) than the natural one, had the typical macroscopic appearance of a corpus luteum. Histological examination of the structure using electron microscopy revealed typical structural features of a natural CL. Mean tissue progesterone concentration was significantly lower in the secondary CL (31.15 +/- 3.11 compared with 58.29 +/- 6.32 micrograms/g tissue of the cyclic CL) and oestradiol-17 beta significantly higher than in the natural CL (108 +/- 11.6 compared with 74.2 +/- 7.81 pg/g tissue). P450scc and P450(17 alpha) mRNA was detected in both structures while P450arom and full-length mRNA FSH receptor were detected only in the secondary structure.

Animals↗
PubMed1995

A family of molecules related to collapsin in the embryonic chick nervous system.

Signaling molecules with either attractive or repulsive effects on specific growth cones are likely to play a role in guiding axons to their appropriate targets. A chick brain glycoprotein, collapsin, has been shown to be a good candidate for a repulsive guidance cue. We report here the discovery of four new molecules related to collapsin in chick brains. All contain a semaphorin domain. One is structurally very similar to collapsin but is only 50% identical in its amino acid sequence. We have named it collapsin-2. The collapsin-related genes exhibit distinct but overlapping patterns of mRNA expression in the developing spinal cord and the developing visual system. This family of collapsin-related molecules could potentially act as repulsive cues toward specific neuronal populations.

Amino Acid Sequence↗
PubMed2006

Consequences of unilateral nigrostriatal denervation on the thalamostriatal pathway in rats.

The position of the caudal intralaminar nuclei within basal ganglia circuitry has largely been neglected in most studies dealing with basal ganglia function. During the past few years, there has been a growing body of evidence suggesting that the thalamic parafascicular nucleus in rodents (PF) exerts a multifaceted modulation of basal ganglia nuclei, at different levels. Our aim was to study the activity of the thalamostriatal pathway in rats with unilateral dopaminergic depletion. The experimental approach comprised first unilateral delivery of 6-OHDA in the medial forebrain bundle. Thirty days post-lesioning, animals showing a clear asymmetry were then subjected to bilateral injection of Fluoro-Gold (FG) within the striatum. Subsequently, expression of the mRNA encoding the vesicular glutamate transporter 2 (vGLUT2) was detected within thalamostriatal-projecting neurons (FG-labeled) by in situ hybridization and the results were confirmed by laser-guided capture microdissection microscopy followed by real-time PCR. The data showed that there was a marked neuronal loss restricted to PF neurons projecting to the dopamine-depleted striatum. Moreover, PF neurons innervating the dopamine-depleted striatum were intensely hyperactive. These neurons showed a marked increase on the expression of vGLUT2 mRNA as well as for the mRNA encoding the subunit I of cytochrome oxidase as compared with those neurons projecting to the striatum with normal dopamine content. Thus, the selective neurodegeneration of PF neurons innervating the striatum together with the increased activity of the thalamostriatal pathway coexist after nigrostriatal denervation.

Animals↗
PubMed2006

Up-regulated transforming growth factor beta-inducible gene h3 in rheumatoid arthritis mediates adhesion and migration of synoviocytes through alpha v beta3 integrin: Regulation by cytokines.

OBJECTIVE: To delineate the expression of transforming growth factor beta-inducible gene h3 (betaIG-H3) in rheumatoid synovitis and to determine the regulatory role of betaIG-H3 in the adhesion and migration of fibroblast-like synoviocytes (FLS). METHODS: Synovial tissue was obtained from patients with rheumatoid arthritis (RA) during joint replacement surgery, and FLS were isolated using enzymatic treatment. Immunohistochemical staining was performed to show the expression of betaIG-H3 within rheumatoid synovium. Synthesis of betaIG-H3 from FLS was determined by semiquantitative reverse transcription-polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay. Cell adhesion and migration assays were performed using the YH18 peptide in the fourth fas-1 domain of betaIG-H3 and function-blocking antibodies to integrins. RESULTS: Expression of betaIG-H3 was up-regulated in RA synovial tissue compared with synovial tissue from patients with osteoarthritis. FLS isolated from RA synovial tissue constitutively produced betaIG-H3, which was up-regulated by transforming growth factor beta1, interleukin-1beta, and tumor necrosis factor alpha. Although FLS expressed a variety of integrins, betaIG-H3 mediated adhesion and migration of FLS through interaction with alpha v beta3 integrin. Cytokines failed to affect the betaIG-H3-mediated adhesion. However, migration of FLS guided by betaIG-H3 was enhanced by interferon-gamma and platelet-derived growth factor type BB. The YH18 peptide in the fourth fas-1 domain of betaIG-H3 inhibited adhesion and migration in a dose-dependent manner. CONCLUSION: The results suggest that betaIG-H3, which is abundantly expressed in RA synovial tissue, plays a regulatory role in chronic destructive inflammation through the modulation of the adhesion and migration of FLS. This finding indicates the relevance of betaIG-H3 and alpha v beta3 integrin-interacting motifs as potential therapeutic targets in this disease.

Arthritis, Rheumatoid↗
PubMed1992

Evidence of a tertiary interaction functional in group I 3'-splicing.

It has been recently shown that the schedule of 3'-splicing events for yeast mitochondrial group I introns requires that conserved helix P10 materializes only after 5'-cleavage has taken place. A scenario compatible with experimental findings has been proposed [(1992) FEBS Lett. 297, 201-204; (1990) Proc. Natl. Acad. Sci. USA 87, 8192-8196] where the formation of P10 is postponed by competition for standard base-pairing with an extended P1 interaction engaging the same portion of the internal guide sequence (IGS) which is subsequently involved in P10. Although the formation of P10 in the fifth intron of yeast apocytochrome b gene (YCOB5) has been confirmed by site-directed mutagenesis, we cannot be confident that this interaction is merely stabilized by Watson-Crick base-pairing, involving the 3'-exon and the IGS, especially given that its formation requires closure of an intron loop of 159 unpaired bases. Thus, our aim is to establish the participation of the 5'-extremity of the intron in the formation of P10. By deoxyribose substitution at positions 1 and 2 of the 5'-extremity of the intron, we are able to confirm the existence of tertiary interactions stabilizing the 3'-splicing site. We show that selective deoxyribose substitution renders the intron inefficient for 3'-splicing when compared with wild type levels.

Base Sequence↗
PubMed2007

Screening marine fungi for inhibitors of the C4 plant enzyme pyruvate phosphate dikinase: unguinol as a potential novel herbicide candidate.

A total of 2,245 extracts, derived from 449 marine fungi cultivated in five types of media, were screened against the C(4) plant enzyme pyruvate phosphate dikinase (PPDK), a potential herbicide target. Extracts from several fungal isolates selectively inhibited PPDK. Bioassay-guided fractionation of one isolate led to the isolation of the known compound unguinol, which inhibited PPDK with a 50% inhibitory concentration of 42.3 +/- 0.8 muM. Further kinetic analysis revealed that unguinol was a mixed noncompetitive inhibitor of PPDK with respect to the substrates pyruvate and ATP and an uncompetitive inhibitor of PPDK with respect to phosphate. Unguinol had deleterious effects on a model C(4) plant but no effect on a model C(3) plant. These results indicate that unguinol inhibits PPDK via a novel mechanism of action which also translates to an herbicidal effect on whole plants.

DNA, Fungal↗
PubMed2026

Genomic insights into low-level rifampicin resistance mediated by borderline rpoB mutations in Mycobacterium tuberculosis: prevalence and phylogeny in Northeast China.

The emergence of low-level rifampicin (RIF) resistance in Mycobacterium tuberculosis poses a challenge to tuberculosis (TB) control, as it often leads to discordance between genotypic resistance detected by molecular assays (e.g., Xpert MTB/RIF) and phenotypic susceptibility in conventional drug susceptibility testing (DST). In this study, we performed whole-genome sequencing (WGS) on 17 clinical isolates from Changchun, Northeast China, which exhibited such discordance. All isolates harbored functional borderline mutations in the rpoB RRDR region, predominantly Leu452Pro and Leu430Pro (29% each), followed by His445Asn (18%). RIF minimum inhibitory concentration (MIC) values ranged from ≤0.25 to 1.0 mg/L, confirming low-level resistance. Notably, 53% (9/17) of the isolates were co-resistant to fluoroquinolones and 24% (4/17) to isoniazid (INH). According to WHO classification, 59% (10/17) were pre-extensively drug-resistant TB (Pre-XDR-TB) or multidrug-resistant TB (MDR-TB). Phylogenetic analysis revealed that 94% (16/17) belonged to the East Asian Beijing lineage (Lineage 2.2.1), with no evidence of recent local transmission. These findings underscore the complexity of low-level RIF resistance and its frequent association with broader drug resistance in a dominant lineage, highlighting the need for integrating MIC and WGS into diagnostic algorithms to guide appropriate treatment and surveillance.IMPORTANCEThe accurate detection of RIF resistance is critical for the management of TB, yet standard phenotypic methods often fail to identify strains with low-level resistance conferred by borderline rpoB mutations. This study provides the first genomic characterization of such discordant isolates in Northeast China, revealing a high prevalence of co-resistance to other key drugs and a strong association with the locally dominant Beijing lineage. The findings emphasize that reliance on phenotypic DST alone may lead to underestimation of drug resistance and inappropriate treatment, potentially contributing to the emergence and spread of Pre-XDR-TB and MDR-TB. Incorporating MIC determination and WGS into routine diagnostics could enhance detection, inform tailored therapy, and improve surveillance of these clinically significant strains.

Mycobacterium tuberculosis↗
PubMed2006

Brain-specific small nucleolar RNAs.

Small nucleolar RNAs (snoRNAs) are a group of noncoding RNAs that function mainly as guides for modification of ribosomal RNAs (rRNAs) and small nuclear RNAs (snRNAs). A subgroup of snoRNAs was found to be predominantly expressed in the brain; and interestingly, these brain-specific snoRNAs (b-snoRNAs) appear not to be involved in modification of rRNAs and snRNAs, raising the question of what their function and targets might be. Expression studies of b-snoRNAs in mice have shown potential involvement of two b-snoRNAs, MBII-48 and MBII-52, in learning and memory. HBII-52, the human homolog of MBII-52, appears to be involved with regulation of 5-HT(2C) receptor subunit mRNA. Furthermore, several reports link the disruption of expression of a specific b-snoRNA, HBII-85, with a neurobehavioral disorder, Prader-Willi syndrome. This paper reviews the current knowledge of the properties, expression, and functions of b-snoRNAs.

Animals↗
PubMed2005

CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death.

The 'help' provided by CD4+ T lymphocytes during the priming of CD8+ T lymphocytes confers a key feature of immune memory: the capacity for autonomous secondary expansion following re-encounter with antigen. Once primed in the presence of CD4+ T cells, 'helped' CD8+ T cells acquire the ability to undergo a second round of clonal expansion upon restimulation in the absence of T-cell help. 'Helpless' CD8+ T cells that are primed in the absence of CD4+ T cells, in contrast, can mediate effector functions such as cytotoxicity and cytokine secretion upon restimulation, but do not undergo a second round of clonal expansion. These disparate responses have features of being 'programmed', that is, guided by signals that are transmitted to naive CD8+ T cells during priming, which encode specific fates for their clonal progeny. Here we explore the instructional programme that governs the secondary response of CD8+ T cells and find that helpless cells undergo death by activation-induced cell death upon secondary stimulation. This death is mediated by tumour-necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Regulation of Trail expression can therefore account for the role of CD4+ T cells in the generation of CD8+ T cell memory and represents a novel mechanism for controlling adaptive immune responses.

Animals↗
PubMed2002

Patterns of elevation of plasma 2'-deoxyuridine, a surrogate marker of thymidylate synthase (TS) inhibition, after administration of two different schedules of 5-fluorouracil and the specific TS inhibitors raltitrexed (Tomudex) and ZD9331.

5-Fluorouracil (5-FU) exerts cytotoxic effects through inhibition of thymidylate synthase (TS) and incorporation of metabolites into RNA. TS inhibition may be greater for infusional 5-FU, with bolus regimens more likely to cause RNA effects. Elevation of plasma 2'-deoxyuridine (dUrd) is a surrogate marker of TS inhibition. Nineteen patients were treated with continuous infusion (CI) 5-FU 300mg/m(2)/day or bolus 5-FU 425mg/m(2)/day plus leucovorin (LV) 20mg/m(2)/day days 1-5. Pretreatment (day 1) and day 2, 3, 4, 5, 8, 15, 22, and 29 plasma samples were assayed for dUrd by reverse-phase high-performance liquid chromatography. In patients treated with bolus 5-FU/LV, dUrd elevation at 24 and 48 h was 235 +/- 125 and 254 +/- 119%, respectively, falling to 138 +/- 58%, 156 +/- 89%, and 92 +/- 25% on days 8, 15, and 22, respectively. dUrd elevation with CI 5-FU was 229 +/- 86% at 24 h and 239 +/- 86, 240 +/- 98%, and 255 +/- 109% at days 15, 22, and 29, respectively. Duration of dUrd elevation was generally less than 8 days for bolus 5-FU/LV. A single dose of raltitrexed (3 mg/m(2)) gave a similar profile to this regimen. ZD9331 (130 mg/m(2), days 1 and 8) gave dUrd elevation for 14 of 21 days, with some recovery prior to day 8. Thus, both 5-FU regimens inhibit TS, and prolonged TS inhibition is achieved by CI 5-FU without significant toxicity. This suggests that the mechanism of antiproliferative toxicity from bolus 5-FU/LV is partly non-TS mediated. These results clarify underlying pharmacodynamic processes and could guide scheduling of 5-FU and TS inhibitors.

Antimetabolites, Antineoplastic↗