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At least 181 records · Page 10Linked to original sources
PubMed2005

Role of spatiotemporal expression of iodothyronine deiodinase proteins in cerebellar cell organization.

Thyroid hormones (TH) play a crucial role in various developmental processes in all vertebrates. The expression of a number of thyroid hormone responsive genes is of critical importance in processes like cell maturation and migration. Since these genes are mostly regulated by binding of the receptor-active TH (T(3)) to the thyroid hormone receptor, the availability of this T(3) is indispensable for correct brain lamination. One important way to regulate local TH availability is via the ontogenetic changes in activating and inactivating iodothyronine deiodinases. The current study was set up to investigate the distribution of type I, type II and type III (D1, D2 and D3) iodothyronine deiodinase protein in the chicken cerebellum at two important developmental ages, namely embryonic day 18 when cerebellar cell migration is fully in progress, and 1 day posthatch, when cerebellar maturation is mostly finished. The results show that the deiodinase proteins are divergently expressed in the cerebellar cell population. D1 and D3 are expressed in the granule cells at E18, whereas D2 is found mostly in the molecular layer and the Purkinje cells at that time. One day posthatch, the expression of D1 is limited to the mature granule cells and that of D3 to the Purkinje cells exclusively, whereas D2 remains clearly present in the molecular layer. Comparison of the deiodinase protein distribution with the expression of TH-responsive proteins involved in cell migration (reelin, disabled protein 1 and tenascin-C) allows speculating about the effect of this spatiotemporal distribution pattern on cerebellar cell communicative pathways.

Amino Acid Transport Systems↗
PubMed2026

Identification and characterization of G protein-coupled receptors in the nocturnal halictid bee Megalopta genalis.

G protein-coupled receptors (GPCRs) are one of the largest families of membrane proteins in insects, regulating vision, neural signal transduction, and various physiological behaviors. Megalopta genalis exhibits a unique facultatively eusocial lifestyle and possesses adaptations for nocturnal activity; however, its GPCR family has not yet been systematically characterized. In this study, we performed genome-wide identification, phylogenetic analysis, and expression profiling of GPCRs in M. genalis by integrating genomic annotation and transcriptomic analysis. The results showed that a total of 99 GPCRs were identified in the genome of M. genalis, which were classified into four major families. Here, we show that M. genalis has undergone lineage-specific GPCR repertoire remodeling, marked by the expansion of novel orphan receptors and the systematic loss of multiple receptor subtypes, such as the neuropeptide receptors MIP-R and NPFR. Moreover, opsins have formed a diverse array of combinations and non-GPCR odorant receptors have undergone significant expansion via tandem duplication. Together, these features may represent part of the molecular repertoire associated with the adaptation of M. genalis to a nocturnal lifestyle. Furthermore, transcriptomic analysis revealed distinct spatiotemporal expression divergence within each of the Mth/Mthl and Fz GPCR families, suggesting functional specialization across development and adult tissues. This study provides the first systematic identification and initial functional characterization of GPCRs in M. genalis, revealing an evolutionary pattern characterized by the coexistence of contraction and expansion within the GPCR family. These findings lay a foundation for further studies aimed at elucidating the roles of these GPCRs in regulating M. genalis physiology and behavior.

Animals↗
PubMed2006

A new method to remove hybridization bias for interspecies comparison of global gene expression profiles uncovers an association between mRNA sequence divergence and differential gene expression in Xenopus.

The recent sequencing of a large number of Xenopus tropicalis expressed sequences has allowed development of a high-throughput approach to study Xenopus global RNA gene expression. We examined the global gene expression similarities and differences between the historically significant Xenopus laevis model system and the increasingly used X.tropicalis model system and assessed whether an X.tropicalis microarray platform can be used for X.laevis. These closely related species were also used to investigate a more general question: is there an association between mRNA sequence divergence and differences in gene expression levels? We carried out a comprehensive comparison of global gene expression profiles using microarrays of different tissues and developmental stages of X.laevis and X.tropicalis. We (i) show that the X.tropicalis probes provide an efficacious microarray platform for X.laevis, (ii) describe methods to compare interspecies mRNA profiles that correct differences in hybridization efficiency and (iii) show independently of hybridization bias that as mRNA sequence divergence increases between X.laevis and X.tropicalis differences in mRNA expression levels also increase.

Animals↗
PubMed1991

Limited expression of a diverged beta-tubulin gene during soybean (Glycine max [L.] Merr.) development.

We examined the developmental expression of a diverged soybean beta-tubulin gene (designated sb-1), which had been cloned and sequenced previously. A probe specific for the sb-1 gene was constructed from the 3' transcribed untranslated sequence. As a control, a more general probe for beta-tubulin genes and their transcripts was constructed from a highly conserved region of the third exon of another soybean beta-tubulin gene, sb-2. Poly(A)+ RNA, extracted from various soybean tissues and organs, was probed alternatively with the sb-1 gene-specific probe and with the generic beta-tubulin probe. Levels of beta-tubulin transcripts recognized by the generic probe differed by a factor of approximately 3 in the different tissues and organs and varied with the state of organ development. Highest levels were found in young, unexpanded leaves and they decreased as leaf maturation occurred. In contrast, transcripts of sb-1 were nearly undetectable in young leaves, and they increased as leaf maturation occurred. Levels of sb-1 transcript were low in all organs of the light-grown plant examined, except the hypocotyl, where they were approximately 10-fold higher. However, the highest levels of sb-1 transcripts were observed in elongating hypocotyls of etiolated seedlings. Exposure of six-day-old etiolated seedlings to light for 12 hours halted further hypocotyl elongation and brought about a dramatic, nearly 100-fold, decrease in the steady-state level of sb-1 transcripts.

DNA↗
PubMedDate not supplied

Correlation of simultaneous differential gene expression in the blood and heart with known mechanisms of adriamycin-induced cardiomyopathy in the rat.

As the genomes of mammalian species become sequenced and gene functions are ascribed, the use of differential gene expression (DGE) to evaluate organ function will become common in the experimental evaluation of new drug therapies. The ability to translate this technology into useful information for human exposures depends on tissue sampling that is impractical or generally not possible in man. The possibility that the DGE of nucleated cells, reticulocytes, or platelets in blood may present the necessary link with target organ toxicity provides an opportunity to correlate preclinical with clinical outcomes. Adriamycin is highly effective alone and more frequently in combination with other chemotherapeutic agents in the treatment of a variety of susceptible malignancies. Adriamycin-induced cardiomyopathy was examined as an endpoint to measure the utility of DOE on whole blood as a predictor of cardiac toxicity. Statistically significant gene changes were observed between relevant blood and cardiac gene profiles that corroborated the accepted mechanisms of toxicity (oxidative stress, effects on carnitine transport, DNA intercalation). There were, however, clear indications that other target organs (bone marrow and intestinal tract) were affected. The divergent expression of some genes between the blood and the heart on day 7 may also indicate the timing and mechanism of development of the cardiomyopathy and confirm current therapeutic approaches for its prevention. The data demonstrate that whole blood gene expression particularly in relation to oxidative stress, in conjunction with standard hematology and clinical chemistry, may be useful in monitoring and predicting cardiac damage secondary to adriamycin administration. Appendices A & B, referenced in this paper, are not printed in this issue of Toxicologic Pathology. They are available as downloadable text files at http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. To access them, click on the issue link for 30(4), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org.

Acetyltransferases↗
PubMed2004

Transcriptional similarities, dissimilarities, and conservation of cis-elements in duplicated genes of Arabidopsis.

In plants, duplication of individual genes, long chromosomal regions, and complete genomes provides a major source for evolutionary innovation. We investigated two different types of duplications, tandem and segmental duplications, in Arabidopsis for correlation, conservation, and differences of expression characteristics by making use of large genome-wide expression data as measured by the massively parallel signature sequencing method. Our analysis indicates that large fractions of duplicated gene pairs still share transcriptional characteristics. However, our results also indicate that expression divergence occurs frequently between duplicated gene pairs, a process which frequently might be employed for the retention of sequence redundant gene pairs. Preserved overall similarity between promoters of duplicated genes as well as preservation of individual cis-elements within the respective promoters indicates that the process of transcriptional neo- and subfunctionalization is restricted to only a fraction of cis-elements. We show that sequence similarities and shared regulatory properties within duplicated promoters provide a powerful means to undertake large-scale cis-regulatory element identification by applying an intragenomic phylogenetic footprinting approach. Our work lays a foundation for future comparative studies to elucidate the molecular manifestation of regulatory similarities and dissimilarities of duplicated genes.

Arabidopsis↗
PubMed1994

G proteins in rat liver proliferation during cholestasis.

Liver proliferation appears to be dually regulated, in part by cyclic AMP levels. Here we studied the alterations in the stimulatory action of cholera toxin and other agents on the adenylyl cyclase system, as well as the status of Gs and Gi protein subunits during the liver proliferation that follows bile duct ligation in rats. The stimulatory effects of glucagon and vasoactive intestinal peptide (which act through membrane receptors) or guanosine 5'-[beta gamma-imido]triphosphate (which interacts with G proteins) and forskolin (which directly activates the adenylyl cyclase catalytic subunit) on liver adenylyl cyclase activity were blunted in cholestasis. The results indicated an impairment in the stimulatory interaction between the alpha s subunit of Gs protein and the adenylyl cyclase catalytic subunit. Indeed, we observed an important decrease in the stimulation of adenylyl cyclase activity by cholera toxin in cholestasis that was accompanied by a reduced extent of [32P]ADP ribosylation of alpha s protein catalyzed by cholera toxin, as revealed by the poor labeling of the 42,000 Da band in liver membranes from cholestatic rats. However, there was no change in the amount of alpha s or beta proteins as measured with immunoblotting techniques. Experiments on [32P]ADP ribosylation of alpha i subunits of Gi proteins indicated an impairment in liver membranes from cholestatic rats, whereas Western blotting for the detection of alpha i subunits showed decreased alpha i3 and increased alpha i2 levels in this condition. Further efforts are needed to better understand the molecular mechanisms underlying the relationship between the observed divergent expression of Gs and Gi proteins and liver cell proliferation in the cholestatic liver.

Adenosine Diphosphate↗
PubMed2026

Wolbachia strain wLhui induces temperature-dependent incomplete cytoplasmic incompatibility in the invasive pest Liriomyza huidobrensis with biocontrol potential.

BACKGROUND: Wolbachia is a maternally inherited endosymbiont that manipulates host reproduction through cytoplasmic incompatibility (CI), offering promising opportunities for biocontrol of agricultural pests. The leaf-miner Liriomyza huidobrensis (Blanchard) is a globally invasive and highly polyphagous pest with a high incidence of Wolbachia infection; however, its reproductive effects remain poorly understood. Here, we investigated the reproductive manipulation induced by the Wolbachia strain wLhui using genomics analyses and crossing assays. RESULTS: wLhui localized primarily to the reproductive tissues of both female and male adults and maintained a 100% infection prevalence across three host generations under both low (15 and 20 °C) and moderate (25 °C) temperatures. Crossing assays showed that wLhui induced incomplete CI, reducing egg hatch by approximately 30% in incompatible crosses. Both CI strength (sh) and wLhui density varied with host rearing temperature. Genome sequencing revealed that wLhui (approximately 1.27 Mb) belongs to supergroup A and harbors two pairs of CI factor genes (cifA and cifB). These Cif proteins are classified as Type I and exhibit substantial phylogenetic and structural divergence. Expression of CifB-pair1 caused growth defects in yeast, suggesting that CifB-pair1 exhibits toxicity. However, no direct interaction between CifA and CifB was detected by yeast two-hybrid assays. CONCLUSIONS: These findings elucidate the role and molecular basis of wLhui-induced reproductive manipulation and highlight its potential for developing Wolbachia-based biocontrol strategies against leaf-miner pests. © 2026 Society of Chemical Industry.

Animals↗
PubMed1995

Nag repressor-operator interactions: protein-DNA contacts cover more than two turns of the DNA helix.

The NagC repressor binds to two sites in the intergenic nagE-B region overlapping the divergently expressed nagE and nagB promoters. In addition the NagC repressor binds to two sites upstream of the manXYZ operon. Although basically palindromic, there is little sequence consensus between the four operators. To identify the DNA sequence important for NagC recognition, we have taken advantage of the fact that repression of the nagE and nagB genes requires the formation of a loop of DNA between molecules of the repressor bound to the nagE and nagB operators. The nagE operator was systematically mutagenised and the effect of the mutations measured on the level of expression from a nagB-lacZ fusion. These experiments showed that the most important positions for recognition are the two A.T base-pairs at positions-5 and -6 from the centre of symmetry. These are the only absolutely conserved bases in the four operators. Certain changes of residues at position -3 and -4 have fairly strong effects while changes at -7 to -10 have only minor effects. However the presence of a G or C base at positions + 11 or -11 produces a NagC binding site with considerably higher affinity than the wide-type nagE operator both in vitro and in vivo, a "super-operator". The presence of a super-operator considerably increased the stability of the binary looped NagC-DNA complex in vitro. However in the presence of cAMP/CAP, NagC showed the same apparent binding affinity to wild-type and super-operators indicating that one role of cAMP/CAP in the repression complex is to reduce the need for high affinity sites. These super-operators allow a higher level of repression of the nagE promoter compared to the nagB, presumably due to the existence of linear complexes of NagC bound to BoxE.

Bacterial Proteins↗
PubMed1995

A two-reporter gene system for the analysis of bi-directional transcription from the divergent MAL6T-MAL6S promoter in Saccharomyces cerevisiae.

Many sets of genes in Saccharomyces cerevisiae are divergently transcribed, but at present there are no vectors generally available for the simultaneous analysis of divergent transcription from these promoters. In the present study MEL1 and lacZ were used to construct a vector capable of measuring the divergent expression initiated by the MAL6T-MAL6S bi-directional promoter. Our observations demonstrate that the expression of both reporter genes was regulated in a similar fashion to the native MAL6T and MAL6S genes, and that induction was dependent upon the presence of a functional MALR activator gene. The results confirmed that the MAL6T-MAL6S promoter was co-ordinately regulated, repressed by glucose, induced by maltose, and that basal expression was more active in the MAL6S direction than in the MAL6T direction.

Genes, Reporter↗
PubMed1997

Overexpression of cyclin B1 in human colorectal cancers.

The expression of the human cyclin B1 gene was investigated with Western blot analysis in human colorectal carcinomas and in adjacent non-neoplastic colorectal mucosas. Out of 41 cancers, 36 (88% of patients) showed much higher expression of cyclin B1 than did the non-neoplastic mucosa. Proliferating-cell nuclear antigen (PCNA) immunohistochemistry revealed that the labeling indexes of these cancer tissues were 47.3 +/- 11.3% while those of the mucosa were 15.6 +/- 5.5%. Only 5 cancers (12% patients) demonstrated the same expression level of cyclin B1 as the mucosa; however, the PCNA labeling indexes were 42.3 +/- 11% for the cancer tissue, compared to 12.6 +/- 2.4% for the mucosas. Southern blot analysis showed that there was no change of the cyclin B1 gene at the somatic DNA level in spite of its high expression at the protein level. These results proved that majority of colorectal cancers express high levels of cyclin B1, consistent with a high rate of cell proliferation, whereas a small fraction of these cancers lose control of cyclin B1 expression, diverging from their fast cell proliferation.

Adenocarcinoma↗
PubMed2004

Agonistic onset during development differentiates wild house mouse males (Mus domesticus).

Wild house mouse populations have been suggested to locally adapt to varying dispersal regimes by expressing divergent aggressivity phenotypes. This conjecture implies, first, genetic polymorphism for dispersive strategies which is supported by the finding of heritable variation for male dispersal tendency in feral house mice. Secondly, aggressivity is assumed to translate into dispersal rates. This speculation is reinforced by experimental evidence showing that non-agonistic males display lower dispersal propensity than same-aged males that have established agonistic dominance. However, the actual ontogenetic behavioural pattern and its variability among populations remain unknown. Hence, in this study the timing of agonistic onset is quantified within laboratory-reared fraternal pairs, and compared between descendants from two different feral populations. Males from the two populations (G and Z) differed strongly in agonistic development, as Z fraternal pairs had a 50% risk of agonistic onset before 23.5+/-2.7 days of age, while this took 57.3+/-5.4 days in males from population G. This difference coincided with significant genetic differentiation between the males of the two populations as determined by 11 polymorphic microsatellite markers. Furthermore, in population G, males from agonistic and amicable fraternal pairs exhibited significant genetic differentiation. These results corroborate the supposition of genetic variability for dispersive strategies in house mice, and identify the ontogenetic timing of agonistic phenotype development as the potential basis for genetic differentiation. This opens a unique opportunity to study the genetic determination of a complex mammalian behavioural syndrome in a life history context, using a simple laboratory paradigm.

Animals↗
PubMed2026

Impaired leptin A signaling disrupts hepatic lipid metabolism and growth in female medaka (Oryzias latipes).

Leptin is a central regulator of appetite and energy metabolism in vertebrates, and its deficiency in mammals typically results in hyperphagia and severe obesity. In fish, however, the physiological roles of leptin remain less clearly defined, partly due to the whole genome duplication (WGD) and divergent expression patterns. In this study, we generated a leptin A (lepa) loss-of-function mutant in medaka (Oryzias latipes) using CRISPR/Cas9 to investigate the function of leptin signaling. Phenotypic analysis revealed that female homozygous mutants exhibited significantly reduced body length and body weight compared with wild-type females, indicating growth impairment. Unexpectedly, despite their lean phenotype, the female mutants developed pronounced hepatic steatosis accompanied by the formation of spongiosis hepatis structures, while no obvious fibrosis was detected. To explore the molecular mechanisms underlying these abnormalities, transcriptomic profiling of mutant livers was performed. Differentially expressed genes were significantly enriched in pathways related to lipid metabolism, including Fatty acid metabolism and PPAR signaling pathway, suggesting a potential reduction in hepatic fatty acid β-oxidation capacity. In addition, genes involved in endoplasmic reticulum stress, autophagy, and apoptosis were altered, indicating transcriptional changes in cellular stress-response pathways under leptin A deficiency. Together, these findings suggest that leptin A may play an important role in coordinating growth and hepatic lipid metabolism in medaka and highlight potential differences in leptin-mediated metabolic regulation between fish and mammals.

Animals↗
PubMed1994

Neurokinin receptor subtypes characterized by biological assays.

Neurokinin receptors have been characterized by biological assays using naturally occurring and selective agonists as well as peptide and non peptide antagonists. Six preparations have been used: the rabbit vena cava and the rat urinary bladder, treated with a NK-2 receptor antagonist for the NK-1 receptor, the rabbit pulmonary artery and the hamster urinary bladder for the NK-2, the rat portal vein and the guinea pig ileum, treated with a NK-1 receptor antagonist, for the NK-3. Treatment with antagonists was required because of the presence (in some preparations) of two functional sites contributing to the biological effect. Differences in the order of potency of agonists between each couple of receptors have been demonstrated, especially with tachykinins and the selective agonists. Such differences are even more evident with antagonists, some of which show apparent affinity (pA2) values 1.5 to 3 log units higher in one than in the other member of each couple. Based on data obtained in pharmacological experiments, it is concluded that NK-1, NK-2 and NK-3 receptors show differences strong enough to justify the assumption that their coding and/or expression diverge among species.

Animals↗
PubMed2003

Expansion of the BPI family by duplication on human chromosome 20: characterization of the RY gene cluster in 20q11.21 encoding olfactory transporters/antimicrobial-like peptides.

Antimicrobial peptides provide a defense system against microorganisms. One class of these molecules binds lipophilic substrates and is therefore directed against gram-negative bacteria. This family includes proteins related to bactericidal/permeability-increasing protein (BPI). We characterized an approximately 100-kb cluster of three human genes named RYSR, RYA3, and RY2G5 that are related to the BPI family. The RY cluster maps to 20q11.21, >5 Mb upstream of the BPI cluster. The RY and BPI genes have similar exon structures, indicating that they were derived by duplication from a common ancestor. We identified mouse BPI-related and RY orthologues in syntenic regions, indicating that the gene family expanded before mouse and human diverged. Expression analyses show that RYs are strongly expressed in the olfactory epithelium, suggesting that they also could act as odorant transporters or detoxification agents in the olfactory system. Together, these data show how mammals diversified their antimicrobial defenses/olfactory pathways through a duplication-driven adaptive selection process.

Amino Acid Sequence↗
PubMed1993

The pulmonary artery (Swan-Ganz) catheter. Evaluation of a hemodynamic monitoring device in critical care medicine.

The pulmonary artery catheter (PAC) is an invasive hemodynamic monitoring device that is used extensively in critical care units. This technological advance allows the critical care physician and nurse to closely monitor physiological functions at the bedside. There have been no formal evaluations of the impact of this device on patient care. Reviews and observational studies have yielded different conclusions regarding risks and benefits to patients. This has resulted in much editorial comment expressing divergent opinions on the value of the PAC, but there has been no scientific evidence to guide practice and no apparent effect on the use of these devices. The PAC and other medical monitoring devices must be evaluated with respect to their impact on patient care.

Catheterization, Swan-Ganz↗
PubMed2001

The participation of AtXPB1, the XPB/RAD25 homologue gene from Arabidopsis thaliana, in DNA repair and plant development.

Nucleotide excision repair in Arabidopsis thaliana differs from other eukaryotes as it contains two paralogous copies of the corresponding XPB/RAD25 gene. In this work, the functional characterization of one copy, AtXPB1, is presented. The plant gene was able to partially complement the UV sensitivity of a yeast rad25 mutant strain, thus confirming its involvement in nucleotide excision repair. The biological role of AtXPB1 protein in A. thaliana was further ascertained by obtaining a homozygous mutant plant containing the AtXPB1 genomic sequence interrupted by a T-DNA insertion. The 3' end of the mutant gene is disrupted, generating the expression of a truncated mRNA molecule. Despite the normal morphology, the mutant plants presented developmental delay, lower seed viability and a loss of germination synchrony. These plants also manifested increased sensitivity to continuous exposure to the alkylating agent MMS, thus suggesting inefficient DNA damage removal. These results indicate that, although the duplication seems to be recent, the features described for the mutant plant imply some functional or timing expression divergence between the paralogous AtXPB genes. The AtXPB1 protein function in nucleotide excision repair is probably required for the removal of lesions during seed storage, germination and early plant development.

Arabidopsis↗
PubMed1999

Biosynthesis of osteogenic growth peptide via alternative translational initiation at AUG85 of histone H4 mRNA.

The osteogenic growth peptide (OGP) is an extracellular mitogen identical to the histone H4 (H4) COOH-terminal residues 90-103, which regulates osteogenesis and hematopoiesis. By Northern analysis, OGP mRNA is indistinguishable from H4 mRNA. Indeed, cells transfected with a construct encoding [His102]H4 secreted the corresponding [His13]OGP. These results suggest production of OGP from H4 genes. Cells transfected with H4-chloramphenicol acetyltransferase (CAT) fusion genes expressed both "long" and "short" CAT proteins. The short CAT was retained following an ATG --> TTG mutation of the H4 ATG initiation codon, but not following mutation of the in-frame internal ATG85 codon, which, unlike ATG1, resides within a perfect context for translational initiation. These results suggest that a PreOGP is translated starting at AUG85. The translational initiation at AUG85 could be inhibited by optimizing the nucleotide sequence surrounding ATG1 to maximally support upstream translational initiation, thus implicating leaky ribosomal scanning in usage of the internal AUG. Conversion of the predicted PreOGP to OGP was shown in a cell lysate system using synthetic [His102]H4-(85-103) as substrate. Together, our results demonstrate that H4 gene expression diverges at the translational level into the simultaneous parallel production of both H4, a nuclear structural protein, and OGP, an extracellular regulatory peptide.

Animals↗