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Results for “segmentation clock”

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PubMed1997

[Development of corneal sensitivity after phacoemulsification with scleral tunnel incision].

BACKGROUND: after anterior segment surgery the anatomical structures and in particular corneal metabolism and corneal trophic are reduced. The corneal wound healing might be monitored by measuring corneal sensitivity. MATERIAL AND METHOD: In a prospective study of 1 year corneal sensation of 26 patients, age = 72.49 +/- 11.09 years, after phacoemulsification with scleral tunnel is examined. Corneal sensitivity is measured with the Draeger aesthesiometer in the corneal center, in the 6 o'clock and 12 o'clock position before and 4 weeks, 4 months and 1 year after the operation. RESULTS: The preoperative corneal sensitivity thresholds before the operation are with 11.61 +/- 10.49 x 10(-5) N in the 12 o'clock position, in the center with 2.43 +/- 2.57 x 10(-5) N and in the 6 o'clock position with 11.86 +/0 10.37 x 10(-5) N normal. Even 1 year after surgery corneal sensitivity is markedly reduced with 257.08 +/- 306.71 x 10(-5) N, 107.77 +/- 246.76 x 10(-5) N and 82.81 +/- 140.77 x 10(-5) N in the 6 o'clock position. CONCLUSION: Even 1 year after phacoemulsification corneal sensitivity is definitely hyposensitive in the center and descretely hypotensitive in the periphery at the 6 o'clock.

Adult↗

PubMedDate not supplied

Product of per locus of Drosophila shares homology with proteoglycans.

Genes controlling biological rhythms have been identified in Drosophila. The best characterized of these genes is called period (per). Although wild-type flies have daily (circadian) rhythms with a periodicity of approximately 24 h, pers and per1 mutants have 19-h and 29-h rhythms, respectively, and pero mutants are arrhythmic. The pers mutation also enhances the sensitivity of the circadian clock to resetting by light stimuli, and all three types of per mutations affect a much shorter period ultradian rhythm, the 55-s rhythm of the Drosophila courtship song. A fragment of DNA of approximately 7 kilobases (kb) encoding a 4.5-kb poly(A)+ RNA restores rhythmicity when transduced into Drosophila carrying mutations or chromosomal deletions of the per locus. Here we report the sequence of this biologically active segment of DNA. The transcription unit that encodes the 4.5-kb RNA has been mapped, permitting a conceptual translation of a protein of 1,127 amino acids. Several abnormal phenotypes characterized by long-period rhythms are associated with changes in the sequence of untranslated portions of the transcription unit. The structure of some segments of the predicted protein suggests that it is a proteoglycan.

Amino Acid Sequence↗

PubMed1985

DNA repair, antibody diversity, and aging.

Proposed relationships of DNA repair, mutation, and the process of generation of antibody diversity allow new insights into the mechanism of aging. Pathways of antibody development are reviewed with special attention to steps which generate diversity. The normal process of combinatorial fusion of V region gene segments (i.e. V, D, and J) coding for the entire V region, plus the somatic variation within the fusing sites, appear to be enough to account for adequate antibody diversity without a hypermutation mechanism. We propose that the somatic hypermutation commonly observed in antibody V regions may have limited usefulness to expand the diversity of the antigen-binding capacity of the individual. Rather, such mutation may serve as a time clock for aging. Knowledge about humans with specific abnormal repair and/or mutation functions will allow testing of this proposal.

Aging↗

PubMed1998

Eggs and embryos from the Cambrian.

The early evolution of metazoans is a major focus of biological attention, but is the historical record revealed in the Cambrian "explosion" an accurate reflection of original events? The key questions concern the nature of the earliest animals and when they originated. One widely-mooted suggestion is that planktotrophic larvae, typified by the annelidan trochophore and echinoid pluteus, existed long before the metazoan radiations evident in the Cambrian fossil record. This idea could be consistent for recent evidence of divergence times, based on molecular "clocks," of phyla appearing well before the Cambrian. Now a surprising new discovery of eggs with blastomeres and embryos with well-defined anatomy from the Cambrian (c.530 Myr ago) of China and Siberia promises to extend the arena of debate. In one case a convincing ontogeny can be traced from eggs to adult tube-dwelling cnidarians. In the other example a possible protostome, unhatched and wrapped around the egg, shows segmentation and possibly nascent sclerites. In both, these cases development is direct, i.e., there is no evidence for any planktotrophic larval stage. The implications for our perceptions of both the Cambrian 'explosion' and metazoan phylogeny could be considerable.

Animals↗

PubMedDate not supplied

Diurnal rhythm of cone opsin expression in the teleost fish Haplochromis burtoni.

The biochemical and morphological specializations of rod and cone photoreceptors reflect their roles in sight. The apoprotein opsin, which converts photons into chemical signals, functions at one end of these highly polarized cells, in the outer segment. Previous work has shown that the mRNA of rod opsin, the opsin specific to rods, is renewed in the outer segment with a diurnal rhythm in the retina of the teleost fish Haplochromis burtoni. Here we show that in the same species, all three cone opsin mRNAs (blue, green, and red) also have a diurnal rhythm of expression. Quantitative real-time polymerase chain reaction (PCR) with primer pairs specific for the cone photoreceptor opsin subtypes was used to detect opsin mRNA abundance in animals sacrificed at 3-h intervals around the clock. All three cone opsins were expressed with diurnal rhythms similar to each other but out of phase with the rod opsin rhythm. Specifically, cone opsin expression occurs at a higher level near the onset of the dark period, when cones are not used for vision. Finally, we found that the rhythm of cone opsin expression in fish appears to be light dependent, as prolonged darkness changes normal diurnal expression patterns.

Animals↗

PubMed2001

Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees.

To study the genomic divergences among hominoids and to estimate the effective population size of the common ancestor of humans and chimpanzees, we selected 53 autosomal intergenic nonrepetitive DNA segments from the human genome and sequenced them in a human, a chimpanzee, a gorilla, and an orangutan. The average sequence divergence was only 1.24% +/- 0.07% for the human-chimpanzee pair, 1.62% +/- 0.08% for the human-gorilla pair, and 1.63% +/- 0.08% for the chimpanzee-gorilla pair. These estimates, which were confirmed by additional data from GenBank, are substantially lower than previous ones, which included repetitive sequences and might have been based on less-accurate sequence data. The average sequence divergences between orangutans and humans, chimpanzees, and gorillas were 3.08% +/- 0.11%, 3.12% +/- 0.11%, and 3.09% +/- 0.11%, respectively, which also are substantially lower than previous estimates. The sequence divergences in other regions between hominoids were estimated from extensive data in GenBank and the literature, and Alus showed the highest divergence, followed in order by Y-linked noncoding regions, pseudogenes, autosomal intergenic regions, X-linked noncoding regions, synonymous sites, introns, and nonsynonymous sites. The neighbor-joining tree derived from the concatenated sequence of the 53 segments--24,234 bp in length--supports the Homo-Pan clade with a 100% bootstrap value. However, when each segment is analyzed separately, 22 of the 53 segments (approximately 42%) give a tree that is incongruent with the species tree, suggesting a large effective population size (N(e)) of the common ancestor of Homo and Pan. Indeed, a parsimony analysis of the 53 segments and 37 protein-coding genes leads to an estimate of N(e) = 52,000 to 96,000. As this estimate is 5 to 9 times larger than the long-term effective population size of humans (approximately 10,000) estimated from various genetic polymorphism data, the human lineage apparently had experienced a large reduction in effective population size after its separation from the chimpanzee lineage. Our analysis assumes a molecular clock, which is in fact supported by the sequence data used. Taking the orangutan speciation date as 12 to 16 million years ago, we obtain an estimate of 4.6 to 6.2 million years for the Homo-Pan divergence and an estimate of 6.2 to 8.4 million years for the gorilla speciation date, suggesting that the gorilla lineage branched off 1.6 to 2.2 million years earlier than did the human-chimpanzee divergence.

Alu Elements↗

PubMedDate not supplied

[Asymptomatic myocardial ischemia in the dynamics of anaprilin and korinfar treatment].

Overall thirty-eight patients with exertional angina who had episodes of asymptomatic change of position of T-segment were examined. The above patients were divided into two groups: group I was placed on anaprilin treatment (80-120 mg daily), group II received corinfar (60 mg daily). Episodes of asymptomatic ischemia of the myocardium (AIM) showed two peaks in their 24 h-span occurrence, with the greatest number of these being recordable in early morning hours (from six a.m. to noon), somewhat less--within the time span 12 o'clock-0.6 p.m. Anaprilin monotherapy is more effective than corinfar monotherapy in respect to reduction of AIM episodes occurrences. However, corinfar, unlike anaprilin, prevented the appearance of the evening peak of episodes of "silent" ischemia.

Adrenergic beta-Antagonists↗

PubMed2002

Melatonin synthesis enzymes in Macaca mulatta: focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87).

Arylalkylamine N-acetyltransferase (AANAT; serotonin N-acetyltransferase, EC 2.3.1.87) plays a unique transduction role in vertebrate physiology as the key interface between melatonin production and regulatory mechanisms. Circulating melatonin is elevated at night in all vertebrates, because AANAT activity increases in the pineal gland in response to signals from the circadian clock. Circadian regulation of melatonin synthesis is implicated in a variety of human problems, including jet lag, shift work, insomnia, and abnormal activity rhythms in blind persons. In this report AANAT was studied in the rhesus macaque to better understand human melatonin regulation. AANAT mRNA is abundant in the pineal gland and retina, but not elsewhere; AANAT mRNA is uniformly distributed in the pineal gland, but is limited primarily to the photoreceptor outer segments in the retina. Day and night levels of pineal and retinal AANAT mRNA are similar. In contrast, AANAT activity and protein increase more than 4-fold at night in both tissues. The activity of hydroxyindole-O-methyltransferase, the last enzyme in melatonin synthesis, is tonically high in the pineal gland, but is nearly undetectable in the retina; hydroxyindole O-methyltransferase mRNA levels exhibited a similar pattern. This supports the view that the source of circulating melatonin in primates is the pineal gland. The discovery in this study that rhesus pineal AANAT mRNA is high at all times is of special importance because it shows that posttranscriptional control of this enzyme plays a dominant role in regulating melatonin synthesis.

Acetylserotonin O-Methyltransferase↗

PubMed1988

The chamber angle in exfoliation syndrome. Clinical and pathological findings.

The clinical picture of the chamber angle in capsular glaucoma is described. One or more waves of pigment overpass Schwalbe's line and accumulate on the posterior face of the cornea. These waves are found in the chamber angle between 4 and 8 o'clock across 6 o'clock. The pathological anatomy of the chamber angle in the exfoliation is studied with light microscopy, scanning electronmicroscopy and transmission electronmicroscopy in relation with the material of pseudoexfoliation and pigment granules and the difference with the pigmentary glaucoma is shown.

Anterior Chamber↗

PubMedDate not supplied

Electrophysiologic identification of the location of the colonic pacemakers in humans: further study.

We recently defined the sites of four colonic pacemakers that appear to generate the electric waves assumed to be responsible for the colonic motility. We hypothesized that a dysfunction of one or more of these pacemakers might interfere with the generation of electric waves and the colonic motility. This hypothesis was investigated in the current communication. The tests were performed during the repair of huge incisional hernia of 8 subjects (5 F, 3 M; mean age 42.8 +/- 3.3 SD years). Two electrodes were applied to each of the terminal ileum (TI), cecum (C), and ascending (AC), transverse (TC), descending (DC), and sigmoid (SC) colon. The electric activity of the TI and the various colonic segments was recorded using surface silver-silver chloride electrodes applied to the colon. The site of change of the wave variables between the TI and the C and between the different other colonic segments was determined by changing the position of the electrodes placed over the segments to be examined. Presumably, the sites where the wave variables changed represent the potential location of the pacemakers. We anesthetized these sites individually by injection of 2% Xylocaine, and then recorded the electric activity after 20 min in all the subjects and after 2 h in only 5 subjects. Electric waves in the form of pacesetter and action potentials were recorded from the TI and the colon. The sites of potential pacemakers could be defined at the ileocecal and cecocolonic junctions, at the mid third of the TC, and at the colosigmoid junction. Anesthetization of the cecal pole resulted in disappearance of the cecal electric waves, with persistence of the waves from the other colon segments. Anesthetization of the cecocolonic junction eliminated the electric waves of the AC and the right half of the TC, while the waves in the rest of the colon persisted. The remaining two pacemaker sites produced similar results when anesthetized. The electric waves reappeared after the anesthetic effect had waned. Thus, the colon possesses at least four pacemakers that appear to mediate the colonic motor activity. Individual pacemaker block by anesthetization effected disappearance of electric waves in the relative colonic segment, which reappeared after waning of the anesthetic effect. The disappearance of these waves upon pacemaker anesthetization supports a relationship between the pacemakers at the anesthetized site and the electric waves. The electric waves seem to be generated by these pacemakers. We suggest that colonic inertia, segmental or total, results from the dysfunction of one or more pacemakers, and that an artificial pacemaker could be applied for the treatment of such conditions. These suggestions need to be further studied.

Action Potentials↗

PubMed2001

Preliminary study of the anatomy of the venous drainage of the intrahepatic and extrahepatic bile ducts and its relevance to the practice of hepatobiliary surgery.

BACKGROUND: Although there have been many studies of the arterial supply of the biliary system, attempts to study the corresponding venous drainage have been few and all have been incomplete. The purpose of the present investigation is to describe the anatomy of the venous drainage of both the intrahepatic and extrahepatic bile ducts and to determine its relevance to hepatobiliary surgery. METHODS: The intrahepatic and extrahepatic venous drainage of the bile ducts was investigated in seven specimens by injecting a solution of 10% gelatin coloured with Alcian blue into the portal vein or the superior mesenteric vein to outline the venous drainage. The specimens were dissected under loop magnification and representative drawings were obtained. RESULTS: The surface of the intrahepatic and extrahepatic bile ducts was covered by a fine venous plexus. On the surface of the supraduodenal common hepatic duct and common bile duct the venous plexus drained laterally into marginal veins, usually two in number and known as the 3 o'clock and 9 o'clock marginal veins. Inferiorly the marginal veins and the venous plexus communicated with the pancreaticoduodenal venous plexus, which in its turn drained into the posterosuperior pancreaticoduodenal vein, a branch of the superior mesenteric vein. Superiorly the marginal veins divided into a number of branches. Some branches followed the left and right hepatic ducts into the liver, communicating with the venous plexus and the adjacent branches of the portal vein. Other branches of variable size entered either segment IV or the caudate lobe or process via the hilar venous plexus. A most important finding was that even after dividing the bile duct and all communicating veins at the upper border of the duodenum, the venous plexus and the marginal veins filled normally to the level of transection. This occurred almost certainly by retrograde filling from above. CONCLUSION: The satisfactory results of end-to-end anastomosis in whole liver transplantation depends partly on the presence of adequate venous drainage. This has been amply demonstrated by the injection studies. This would indicate that the poor results of end-to-end repair of the bile duct after surgical trauma results from other factors such as poor technique, devascularization of the cut ends due to trauma, and carrying out the anastomosis under tension. After resection of the hilum for cholangiocarcinoma the venous drainage of the left and right hepatic ducts and their branches depends mainly on the communications between the venous plexus on the ducts and the adjacent branches of the portal vein, even at a lobular or sinusoidal level. The satisfactory results obtained after anastomosis of the left and right hepatic ducts or their branches to a Roux loop ofjejunum attest to this. This applies also to the transplantation of segments II and III in paediatric patients from related adult donors and in patients receiving split liver transplants. Finally, the venous drainage at the bifurcation of the common hepatic duct has been shown to enter the caudate lobe and segment IV directly. This suggests that a hilar cholangiocarcinoma may metastasize to these segments, and perhaps partly explain the significantly better long-term results when the caudate lobe and segment IV are resected en bloc with the cholangiocarcinoma as part of modern radical surgery for this condition.

Bile Duct Neoplasms↗

PubMed2006

Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis.

Regulation of Wnt signaling is essential for embryonic patterning. Sfrps are secreted Wnt antagonists that directly interact with the Wnt ligand to inhibit signaling. Here, we show that Sfrp1 and Sfrp2 are required for anteroposterior (AP) axis elongation and somitogenesis in the thoracic region during mouse embryogenesis. Double homozygous mutations in Sfrp1 and Sfrp2 lead to severe shortening of the thoracic region. By contrast, a homozygous mutation in one or the other exerts no effect on embryogenesis, indicating that Sfrp1 and Sfrp2 are functionally redundant. The defect of a shortened thoracic region appears to be the consequence of AP axis reduction and incomplete somite segmentation. The reduction in the AP axis is partially due to abnormalities in cell migration of pre-somitic mesoderm from the end of gastrulation. Aberrant somite segmentation is associated with altered oscillations of Notch signaling, as evidenced by abnormal Lfng and Hes7 expression during somitogenesis in the thoracic region. This study suggests that Wnt regulation by Sfrp1 and Sfrp2 is required for embryonic patterning.

Animals↗

PubMed1991

Fixation of mutations at the VP1 gene of foot-and-mouth disease virus. Can quasispecies define a transient molecular clock?

The number of nucleotide (nt) substitutions found in the VP1 gene (encoding viral capsid protein) between any two of 16 closely related isolates of foot-and-mouth disease virus (FMDV) has been quantified as a function of the time interval between isolations [Villaverde et al., J. Mol. Biol. 204 (1988) 771-776]. One of them (isolate C-S12) includes some replacements found in isolates that preceded it and other replacements found in later isolates. The study has revealed alternating periods of rapid evolution and of relative genetic stability of VP1. During a defined period of acute disease, the rate of fixation of replacements at the VP1 coding segment was 6 x 10(-3) substitutions per nt per year. Only small differences in the rate of evolution were observed between subsegments within the VP1 gene. The observation of a relatively constant rate of evolution during a disease episode was unexpected. We propose that such constancy may be a consequence of random sampling of mutants from the FMDV quasispecies, followed by their amplification in susceptible hosts (to generate a new quasispecies). Successive sampling and amplification events may result in a steady accumulation of mutations.

Amino Acid Sequence↗

PubMed1988

Unilateral disc-shaped cataract with coloboma of lens.

A case of unilateral disc-shaped cataract with coloboma of the lens is reported. The patient, a 17-year-old girl, had best corrected visual acuity of 0.01 (+ 9 D) in the right eye and 1.2 in the left eye. Exotropia of 10 Hirschberg degrees was found in her right eye. The visual disturbance of that eye was thought to be due to amblyopia. The pupillary center of the lens was very thin and membranous, with no nucleus. A ring-like hypertrophic cataract was observed from the lens equator to the periphery of the pupillary area. A bow-shaped coloboma of the lens was found from 3 to 5 o'clock, where the Zinn's zonule was coarse. Some dozen bright white spots were dispersed temporally from the periphery of the macular ring. This combination of disc-shaped cataract with the coloboma of lens is the first such case reported.

Adolescent↗

PubMed2002

Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop.

Transcription of messenger RNAs (mRNAs) for Notch signaling molecules oscillates with 2-hour cycles, and this oscillation is important for coordinated somite segmentation. However, the molecular mechanism of such oscillation remains to be determined. Here, we show that serum treatment of cultured cells induces cyclic expression of both mRNA and protein of the Notch effector Hes1, a basic helix-loop-helix (bHLH) factor, with 2-hour periodicity. Cycling is cell-autonomous and depends on negative autoregulation of hes1 transcription and ubiquitin-proteasome-mediated degradation of Hes1 protein. Because Hes1 oscillation can be seen in many cell types, this clock may regulate timing in many biological systems.

Acetylcysteine↗

PubMed2003

Cortisol feedback state governs adrenocorticotropin secretory-burst shape, frequency, and mass in a dual-waveform construct: time of day-dependent regulation.

Quantification of in vivo pituitary hormone secretion requires simultaneous appraisal of implicit 1) secretory-burst waveform, mass, and stochastic pulse timing; 2) basal secretion; 3) biexponential elimination kinetics; and 4) random experimental error (Keenan DM, Licinio J, and Veldhuis JD. Proc Natl Acad Sci USA 98: 4028-4033, 2001). The present study extends this analytic formalism to allow for time of day-dependent waveform adaptation (burst-shape change) at statistically determinable boundary times. Thereby, we test the hypothesis that diurnal mechanisms and glucocorticoid negative feedback jointly govern distinctive facets of the burstlike secretion of ACTH. To this end, we reanalyzed intensively (10 min) sampled 24-h plasma ACTH concentration profiles collected previously under feedback-intact and drug-induced cortisol depletion in nine healthy adults. Akaiki information criterion-based model comparison favored dual (rather than single) secretory-burst representation of 24-h ACTH release in both the intact and low-cortisol setting in eight of nine subjects. Under feedback-intact conditions, analytically predicted waveform changepoints (median clock times 0611 and 1739) flanked an interval of elevated ACTH secretory-burst mass (P < 10-3). Experimental hypocortisolemia did not alter day/night boundaries, but 1) stimulated day ACTH secretory-burst mass (P < 10-3); 2) accelerated day ACTH secretory-burst frequency (P < 10-3); and 3) forced skewness of day ACTH secretory bursts toward more rapid initial release (P < 0.05). In contrast, the basal ACTH secretion rate and regularity of interpulse-interval lengths were invariant of day/night segmentation and cortisol availability. In conclusion, unknown diurnal factors and systemic cortisol concentrations codetermine ACTH secretory-burst waveform, frequency, and mass, whereas neither mechanism regulates basal ACTH release or regularity of the burst-renewal process.

Adaptation, Physiological↗

PubMed1996

Endothelium-dependent modulation of pacemaking in lymphatic vessels of the guinea-pig mesentery.

1. Endothelial control of the rate of constrictions and the underlying pacemaker potentials has been studied in vitro in guinea-pig mesenteric lymphatic vessels. 2. ACh stimulated 60% of intraluminally perfused vessels to slow or abolish lymphatic constrictions. This action was inhibited by atropine and was likely to be due to the release of endothelium-derived nitric oxide (EDNO) as the effect was absent after endothelial lysis, mimicked by sodium nitroprusside (SNP), blocked by N omega-nitro L-arginine (NOLA) and partially inhibited by Methylene Blue (MB). 3. The remaining 40% of perfused vessels did not mechanically respond to ACh or SNP. In four of seven such vessels this appeared to be due to excessive perfusion-associated release of EDNO, as incubation with NOLA restored the response to SNP. 4. Application of NOLA or MB in perfused vessels significantly increased constriction frequency, further indicating perfusion-associated release of EDNO. 5. ACh induced a marked increase in endothelial [Ca2+]i of both mechanically responding and non-responding vessels. This ACh-induced increase could be repetitively induced when Ca2+ was present in the perfusate, but rapidly ran down when a Ca(2+)-free EGTA perfusate was used. 6. Intracellular recordings from the smooth muscle of non-perfused vessel segments demonstrated an ACh-induced hyperpolarization and decrease in membrane resistance, changes which were prevented by atropine, NOLA, MB and endothelial lysis and mimicked by SNP. 7. ACh directly reduced the size of the underlying pacemaker potentials termed spontaneous transient depolarizations (STDs). 8. NOLA and MB enhanced STDs in non-perfused vessel segments indicating an endogenous release of EDNO. 9. It is concluded that the lymphatic endothelium produces and releases EDNO endogenously, during perfusion or after stimulation with ACh, to decrease the efficacy of STDs to generate action potentials and resultant constrictions.

Acetylcholine↗

PubMed1999

Circadian rhythm of patched1 transcription in the pineal regulated by adrenergic stimulation and cAMP.

The tumor suppressor patched1 (PTC1), a product of the mammalian homologue of the Drosophila segment polarity gene patched, is a receptor for hedgehog (HH) and is crucial for embryonic development. Although little is known about the signal transduction pathways leading to the activation of ptc1, increased ptc1 transcription has always been associated with elevated HH activity and decreased activity of cAMP-dependent protein kinase A. Here, we demonstrate that in the mammalian pineal gland, ptc1 expression exhibits a dramatic diurnal rhythm with peak expression at midnight. ptc1 mRNA expression in the pineal is regulated by a clock mechanism mediated by the superior cervical ganglion. Most importantly, ptc1 transcription can be induced by agents activating the cAMP signal transduction pathway both in vivo and in vitro and appears to be independent of HH signaling.

Adenosine Triphosphatases↗