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At least 1,063 records · Page 59Linked to original sources
PubMed2004

her11 is involved in the somitogenesis clock in zebrafish.

Somitogenesis requires an intricate process of pre-patterning, which is driven by an oscillator mechanism consisting of the Delta-Notch pathway and hairy- (h) and Enhancer of split- [E(spl)] related genes. With the aim of unravelling the complex mechanism of somite pre-patterning, we have conducted an extensive search for h/E(spl)-related genes in the third release of the Danio rerio genomic sequence. We identified 14 new h/E(spl) genes and analysed them by in situ hybridisation for their potential role in the somitogenesis process. We describe here the functional analysis of one of these genes, which we have named her11. her11 is a paralogue of her1 and, similar to her1, is arranged in a head to head fashion with another her gene, namely the previously described her5. It shares an expression in the midbrain-hindbrain boundary with her5, but is in addition cyclically expressed in patterns overlapping those of her1 and her7 and complementary to those of hey1. Furthermore it is expressed in the anterior half of the most caudally formed somites. We show that Delta-Notch pathway genes and fused somites ( fss) are necessary for the control of her11 expression. However, some aspects of the her11 regulation suggest that at least one additional as yet unknown gene of the Delta-Notch cascade is required to explain its expression. Morpholino-oligonucleotide-mediated knockdown of her11 shows that it is involved in the zebrafish somitogenesis clock via an interaction with her1 and her7. We have also studied the role of hey1 by morpholino injection, but could not find a direct function for this gene, suggesting that it reflects the output of the clock rather than being a core component of the mechanism.

Amino Acid Sequence↗
PubMed2001

Identification of target mRNAs for the clock-controlled RNA-binding protein Chlamy 1 from Chlamydomonas reinhardtii.

An endogenous clock regulates the temporal expression of genes/mRNAs that are involved in the circadian output pathway. In the green alga Chlamydomonas reinhardtii, a clock-controlled RNA-binding protein (Chlamy 1) was identified recently, which represents an analog of the circadian trans-acting factor CCTR from the phylogenetically diverse alga Gonyaulax polyedra. In order to identify in C. reinhardtii target mRNAs that can be recognized by Chlamy 1, gel mobility-shift assays and UV-crosslinking experiments were carried out, and revealed that this protein interacts specifically with the 3' untranslated regions of several mRNAs and recognizes them all via a common cis-acting element, composed of at least seven UG repeats. By using competition assays, it was found that the affinity of Chlamy 1 is highest for mRNAs whose products are key components of nitrogen and CO2 metabolism. Since the activities of enzymes involved in nitrogen metabolism vary in a temporal pattern that is opposite in phase to that of Chlamy 1 binding activity, the protein may repress the translation of the cognate mRNAs.

3' Untranslated Regions↗
PubMed2007

Localization of leucomyosuppressin in the brain and circadian clock of the cockroach Leucophaea maderae.

The myosuppressins (X1DVX2HX3FLRFamide), which reduce the frequency of insect muscle contractions, constitute a subgroup of the FMRFamide-related peptides. In the cockroach Leucophaea maderae, we have examined whether leucomyosuppressin (pQDVDHVFLRFamide) is present in the accessory medulla, viz., the circadian clock, which governs circadian locomotor activity rhythms. Antisera that specifically recognize leucomyosuppressin stain one to three neurons near the accessory medulla. MALDI-TOF mass spectrometry has confirmed the presence of leucomyosuppressin in the isolated accessory medulla. Injections of 1.15 pmol leucomyosuppressin into the vicinity of the accessory medulla at various circadian times have revealed no statistically significant effects on the phase of circadian locomotor activity rhythms. This is consistent with the morphology of the myosuppressin-immunoreactive neurons, which restrict their arborizations to the circadian clock and other optic lobe neuropils. Thus, leucomyosuppressin might play a role in the circadian system other than in the control of locomotor activity rhythms.

Animals↗
PubMed2006

Neurohormones as putative circadian clock output signals in the central nervous system of two cricket species.

Antisera to the neuropeptides corazonin (Crz) and crustacean cardioactive peptide (CCAP) and to the diapause hormone (DH) react with small sets of neurones in the cephalic ganglia of the crickets Dianemobius nigrofasciatus and Allonemobius allardi. The distribution of their immunoreactivities is similar in the two species and overlaps with the locations of presumed circadian clock components in the optic lobes, protocerebrum, tritocerebrum, suboesophageal ganglion (SOG) and frontal ganglion. D. nigrofasciatus contains two Crz-immunoreactive (Crz-ir) cells in each optic lobe, six cell groups in the protocerebrum, four in the tritocerebrum, and one in SOG, whereas A. allardi harbours only five Crz-ir groups in the protocerebrum and four in the tritocerebrum. CCAP immunoreactivity occurs in both species in four protocerebrum cell clusters, four tritocerebrum cell clusters, four SOG cell clusters, one frontal ganglion cell cluster, and two optic lobe cell clusters; D. nigrofasciatus possesses two additional cells with unique links to the lamina in the optic lobe. DH-related antigens are present in four cell clusters in the optic lobe, six (D. nigrofasciatus) or eight (A. allardi) in the protocerebrum, four in the tritocerebrum, and three (A. allardi) or five (D. nigrofasciatus) in the SOG. Some of the detected cells also react with antibody to the clock protein Period (PER) or lie close to PER-ir cells. Crickets reared at two different photoperiods do not differ in the distribution and intensity of immunoreactivities. No changes have been detected during the course of diurnal light/dark cycles, possibly because the antisera react with persistent prohormones, whereas circadian fluctuations may occur at the level of their processing or of hormone release. The projection of immunoreactive fibres to several brain regions, the stomatogastric nervous system and the neurohaemal organs indicates multiple functions of the respective hormones.

Animals↗
PubMed2004

Identification of human Clock gene variants by denaturing high-performance liquid chromatography.

The human Clock gene ( hClock) encodes the CLOCK protein essential for the function of the circadian system. We have screened the entire coding region, including the 5' and 3' untranslated regions (UTRs) and the flanking intronic regions, of the hClock gene for sequence variations in 70 unrelated Chinese Singaporeans with denaturing high-performance liquid chromatography (dHPLC). A total of 15 sequence variations were detected, five of which were novel. All involved single base changes. There were 12 substitutions and three insertions/deletions. All except one were found in the introns or the UTRs. Frequencies of the minor allele for all 15 polymorphisms ranged from 0.7% to almost 50%. For the eight sites whose minor allele frequency was found to be at least 10%, pair-wise comparisons revealed that all except one were in almost complete linkage disequilibrium. Our identification of additional single nucleotide polymorphisms in the hClock gene would provide markers whose frequencies could be established in the selected population and used for further analysis of the phenotypic effects. Our results would also be useful for better planning in the selection of polymorphisms for future genetic association studies involving the hClock gene.

CLOCK Proteins↗
PubMed2006

Biologic clocks and the gut.

The gastrointestinal tract displays biologic rhythms in basal gastric acid output, epithelial cell proliferation, gastrointestinal motility, and appetite regulation. Furthermore, the development of gastrointestinal complications after administration of aspirin and after chemo- and radiotherapy for metastatic colon cancer depends on the time of administration. Biologic rhythms are driven by so-called clock genes. Thus, it is conceivable that subsets of genes in the gastrointestinal tract are under clock gene control as well. The purpose of this article is to discuss basic concepts in the studies of biologic rhythms, to review examples of biologic rhythms in the gastrointestinal tract, and to discuss examples of gastrointestinal diseases in which alterations in biologic rhythms may play a pathogenetic role.

Animals↗
PubMed1979

Molecular clocks, molecular profiles, and optimum diets: three approaches to the problem of aging.

It has been hypothesized that the deamidation of glutaminyl and asparaginyl residues serves as a molecular clock for many biological processes including protein turnover, development, and aging. At present, this hypothesis has passed some experimental tests which are necessary but not sufficient for its acceptance. The current state of evidence about deamidation as a molecular clock is discussed. In addition, since the molecular biology of aging, especially in humans, is only partly understood, it is of value to develop quantitative, empirical measures of physiological human age and to use these measures to evaluate alternative human living conditions, especially easily adopted alternatives like variations in diet. This may allow some decrease in the suffering and loss from human aging until such time as molecular biology provides superior and more intellectually satisfying answers. An empirical system which consists of quantitative measurement of several hundred human chemical constituents followed by computerized pattern recognition is described. It is hoped that this system will eventually become an aid in the minimization of the rate of human aging through changes in diet and other factors.

Adult↗
PubMed1976

Biological clocks: endogenous cycles synchronized by subtle geophysical rhythms.

Organismic sensitivity to atmospheric electromagnetic forces, together with usually asymmetrical phase-response systems, have enabled a simple unified explanation of the biological clocks and their timed rhythms. The clocks, endogenous cycles synchronized by subtle geophysical Zeitgeber, are always accurate. The rhythms, freely phase labile, autophase in "constant conditions" to generate a host of overt frequencies.

Atmosphere↗
PubMed1981

A cybernetical model of the internal cellular clock.

A model of a cell-labeling mechanism for the development tree of a multicellular organism is suggested. The cell-labeling information is assumed to originate because the DNA strands are complementary, rather than identical, so a pair of replicated DNA can carry different information content to newly created pairs of chromosomes. This mechanism can serve as an internal cellular clock and as one of the factors involved in the control of cell differentiation. Some possible structures were analyzed by means of the mathematical theory of reliability and compared with the results of Hayflick's experiments on limited cells'lifetime. The external destruction of the clock mechanism can remove limitations on cell's reproductions and is considered as a cause of carcinogenesis; the model exhibits cumulative and threshold effects. The cell-labeling mechanism of the model is able to provide sometimes equivalent labeling for the initial zygote division as a necessary condition for the appearance of monozygote twins; it is most likely that this may occur only for pairs of monozygote twins with the probability equal to an integer power of 1/2.

Animals↗
PubMed2006

Comparison of clock gene expression in SCN, retina, heart, and liver of mice.

In mammals, the suprachiasmatic nuclei (SCN) in the hypothalamus are the site of a central circadian pacemaker, regulating overt rhythms of behaviour and coordinating the rhythmic activity of oscillators in peripheral tissues. Circadian rhythms in all tissues appear to arise from interacting transcriptional-translational feedback loops, involving a core set of clock genes. Whilst it seems likely that there will be broadly similar mechanisms between the central and peripheral oscillators, the extent to which the fine details of gene expression are conserved between different organs has yet to be assessed. In this study, we examine the molecular profile of clock genes within the central SCN pacemaker and peripheral oscillators, identifying differences in phasing, amplitude, waveform, and basal expression levels.

Animals↗
PubMed2006

Molecular analysis of Dec1 and Dec2 in the peripheral circadian clock of zebrafish photosensitive cells.

To elucidate the roles of DEC1 and DEC2, basic helix-loop-helix transcription factors, in the circadian clock of photosensitive zebrafish peripheral cells, zebrafish Dec1 and Dec2 (zDec1 and zDec2) were cloned and their functions and expression patterns were examined in BRF41, a zebrafish cell line. zDEC1 and zDEC2 have high sequence similarity to mammalian counterparts and the molecular phylogenetic analysis of the zDEC1 and zDEC2 sequences reflected the predicted pattern of species classification. zDEC1 and zDEC2 inhibited zCLOCK1:zBMAL3 mediated transcription as CRY1a. zDec1 and zDec2 mRNA showed robust circadian oscillation in BRF41 cells. However, zDec1 and zDec2 mRNA was not strongly induced by exposure to light. These results indicate that zDec1 and zDec2 are involved in the circadian clock mechanism in photosensitive zebrafish peripheral cells by suppressing CLOCK/BMAL-induced gene expression and that the feedback loops of zDEC1 and zDEC2 may be interlocked with the PER/CRY core circadian feedback loops.

Animals↗
PubMed2004

Control of chemical pattern formation by a clock-and-wavefront type mechanism.

The segmentation of many animals ranging from insects to mammals involves the sequential formation of stationary stripes of gene expression that are perpendicular to the growth axis of the developing embryo. This process has been accounted for by a variety of theoretical "clock-and-wavefront" type models that involve the arrest of an oscillation (the clock) at a moving boundary (the wavefront). Here, we demonstrate experimentally that progressive arrest of a homogeneous oscillation can control the symmetry as well as the wavelength of spatial structures in a chemical system. We show how a spontaneously formed, labyrinthine pattern can be converted into a pattern composed of ordered, parallel stripes and confirm a previously predicted proportionality between the wavelength and the period of the homogeneous oscillation. Our experiments provide the first experimental demonstration of a general mechanism for the control of pattern formation that has been hypothesized to operate in the context of biological morphogenesis.

Animals↗
PubMed2004

Bioluminescence imaging of individual fibroblasts reveals persistent, independently phased circadian rhythms of clock gene expression.

Circadian (ca. 24 hr) oscillations in expression of mammalian "clock genes" are found not only in the suprachiasmatic nucleus (SCN), the central circadian pacemaker, but also in peripheral tissues. Under constant conditions in vitro, however, rhythms of peripheral tissue explants or immortalized cells damp partially or completely. It is unknown whether this reflects an inability of peripheral cells to sustain rhythms, as SCN neurons can, or a loss of synchrony among cells. Using bioluminescence imaging of Rat-1 fibroblasts transfected with a Bmal1::luc plasmid and primary fibroblasts dissociated from mPer2(Luciferase-SV40) knockin mice, we monitored single-cell circadian rhythms of clock gene expression for 1-2 weeks. We found that single fibroblasts can oscillate robustly and independently with undiminished amplitude and diverse circadian periods. Cells were partially synchronized by medium changes at the start of an experiment, but due to different intrinsic periods, their phases became randomly distributed after several days. Closely spaced cells in the same culture did not have similar phases, implying a lack of functional coupling among cells. Thus, like SCN neurons, single fibroblasts can function as independent circadian oscillators; however, lack of oscillator coupling in dissociated cell cultures leads to a loss of synchrony among individual cells and damping of the ensemble rhythm at the population level.

Animals↗
PubMed2005

No association of clock gene T3111C polymorphism and affective disorders.

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

Adult↗
PubMed2005

Circadian rhythms in Neurospora crassa: clock gene homologues in fungi.

Computer-based analysis of a total of 17 filamentous fungal and yeasts genomes has shown: (1) homologues of frq, wc-1, wc-2, and vvd, key gene components of the Neurospora crassa clock, are present in Magnaporthe grisea, Gibberella zeae, and Podospora anserina, suggesting an frq-based oscillator in these organisms; (2) some fungal species that are more distantly related to Neurospora, such as Rhizopus oryzae do not appear to have frq homologues; (3) many fungal species that do not appear to contain frq, such as Aspergillus nidulans, do contain wc homologues; (4) of 11 well-described genes classified as clock-controlled genes (ccgs), in Neurospora, all of them were found to have homologues in other fungi; (5) the ccg-8 gene of N. crassa has homologies to opi1p, a transcriptional regulatory gene in Saccharomyces cerevisiae involved in inositol regulation. This suggests the possibilities of rhythmic inositol regulation, and/or a cascade of rhythmic activation of other genes in N. crassa.

Biological Clocks↗
PubMed2004

Drosophila cryb mutation reveals two circadian clocks that drive locomotor rhythm and have different responsiveness to light.

Cryptochrome (CRY) is a blue-light-absorbing protein involved in the photic entrainment of the circadian clock in Drosophila melanogaster. We have investigated the locomotor activity rhythms of flies carrying cryb mutant and revealed that they have two separate circadian oscillators with different responsiveness to light. When kept in constant light conditions, wild-type flies became arrhythmic, while cryb mutant flies exhibited free-running rhythms with two rhythmic components, one with a shorter and the other with a longer free-running period. The rhythm dissociation was dependent on the light intensities: the higher the light intensities, the greater the proportion of animals exhibiting the two oscillations. External photoreceptors including the compound eyes and the ocelli are the likely photoreceptors for the rhythm dissociation, since rhythm dissociation was prevented in so1;cryb and norpAP41;cryb double mutant flies. Immunohistochemical analysis demonstrated that the PERIOD expression rhythms in ventrally located lateral neurons (LNvs) occurred synchronously with the shorter period component, while those in the dorsally located per-expressing neurons showed PER expression most likely related to the longer period component, in addition to that synchronized to the LNvs. These results suggest that the Drosophila locomotor rhythms are driven by two separate per-dependent clocks, responding differentially to constant light.

Animals↗
PubMed2004

A partial hepatectomy results in altered expression of clock-related and cyclic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes.

The liver is among the peripheral organs that display a clear circadian rhythmicity. To investigate whether specific pathological conditions affect circadian rhythms in the liver, we examined the expression profiles of the clock-related and glyceraldehyde 3-phosphate dehydrogenase (GADPH) genes following a partial hepatectomy in the mouse. This surgical procedure causes dynamic proliferation of residual hepatocytes and within one day of the operation the hepatectomized mice demonstrated higher expression of both mPer1 and mPer2 genes in the remaining liver tissue when compared to control mice that had undergone a Sham-operation. In contrast, the mCry1 gene in hepatectomized mice displayed a circadian gene expression profile that was similar to the control group. In addition, GAPDH levels, that demonstrated no oscillations in Sham-hepatectomized mice, underwent daily alterations following a partial hepatectomy. These findings suggest that the regenerative state of the liver affects the expression not only of clock-related genes but also of genes that are constitutively expressed under steady state conditions.

Animals↗
PubMed2004

Amide molecular clocks in drosophila proteins: potential regulators of aging and other processes.

After synthesis and folding, peptides and proteins undergo changes in charge and conformation through nonenzymatic deamidation of asparaginyl and glutaminyl residues. Each amide has a specific deamidation rate that is genetically determined by the sequence of residues immediately adjacent in the peptide chain and by secondary, tertiary, and quaternary structure. By means of experimentally verified computations, we have determined the deamidation rates of 49 Drosophila peptides and proteins. These rates demonstrate that deamidation provides molecular clocks that are suitable for the regulation of Drosophila aging, development, and other biochemical processes. We have also determined the rates of deamidation for 17,886 other proteins from a wide variety of organisms. The distribution function of these deamidation rates demonstrates the suitability of amide residues as biomolecular clocks.

Aging↗