TY - JOUR. T1 - Codon usage affects the structure and function of the Drosophila circadian clock protein PERIOD. AU - Fu, Jingjing. AU - Murphy, Katherine A.. AU - Zhou, Mian. AU - Li, Ying H.. AU - Lam, Vu H.. AU - Tabuloc, Christine A.. AU - Chiu, Joanna C.. AU - Liu, Yi. PY - 2016/8/1. Y1 - 2016/8/1. N2 - Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period (dper), a core clock gene that encodes a critical component of the circadian oscillator, we showed that dper codon usage is important for circadian clock function. Codon optimization of dper resulted in conformational changes of the dPER protein, altered dPER phosphorylation profile and stability, and impaired dPER function in the circadian negative feedback loop, which ...
Circadian clocks can be reset by light stimulation. To investigate the mechanism of this phase shifting, the effects of light pulses on the protein and messenger RNA products of the Drosophila clock gene period (per) were measured. Photic stimuli perturbed the timing of the PER protein and messenger RNA cycles in a manner consistent with the direction and magnitude of the phase shift. In addition, the recently identified clock protein TIM (for timeless) interacted with PER in vivo, and this association was rapidly decreased by light. This disruption of the PER-TIM complex in the cytoplasm was accompanied by a delay in PER phosphorylation and nuclear entry and disruption in the nucleus by an advance in PER phosphorylation and disappearance. These results suggest a mechanism for how a unidirectional environmental signal elicits a bidirectional clock response.. ...
Fig. 1. Interlocked feedback loop model for Drosophila and mouse circadian oscillators. (A) Drosophila. The per/tim loop (left) and dClk loop (right) are shown. The model is based on data from peripheral oscillators. dCLK-CYC heterodimers activate per and tim transcription, and PER and TIM monomers accumulate in the cytoplasm and form heterodimers. PER-TIM then enters the nucleus, binds dCLK-CYC and inhibits the activation of per and tim, thus completing the per/tim feedback loop. dCLK-CYC dimers inhibit dClk transcription either directly (1a/1b) or indirectly via activation of a dClk repressor (2). Repression might occur through protein-DNA interaction (1a/2a) or protein-protein interaction (1b/2b). Repression of dClk is relieved when PER-TIM binds to dCLK-CYC, thus preventing this negative-feedback, and ensuring that per/tim and dClk mRNA transcripts cycle in anti-phase. Light input occurs through CRY, ultimately leading to the degradation of TIM. CRY can bind to TIM and PER, but whether CRY ...
1. Zheng X, Sehgal A (2012) Speed control: cogs and gears that drive the circadian clock. Trends Neurosci 35: 574-585. doi: 10.1016/j.tins.2012.05.007 22748426. 2. Hardin PE (2011) Molecular genetic analysis of circadian timekeeping in Drosophila. Adv Genet 74: 141-173. doi: 10.1016/B978-0-12-387690-4.00005-2 21924977. 3. Rothenfluh A, Young MW, Saez L (2000) A TIMELESS-independent function for PERIOD proteins in the Drosophila clock. Neuron 26: 505-514. 10839368. 4. Curtin KD, Huang ZJ, Rosbash M (1995) Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock. Neuron 14: 365-372. 7857645. 5. Ko HW, Kim EY, Chiu J, Vanselow JT, Kramer A, et al. (2010) A hierarchical phosphorylation cascade that regulates the timing of PERIOD nuclear entry reveals novel roles for proline-directed kinases and GSK-3beta/SGG in circadian clocks. J Neurosci 30: 12664-12675. doi: 10.1523/JNEUROSCI.1586-10.2010 20861372. 6. Chang DC, Reppert SM (2003) A novel C-terminal ...
This new research might unite neurobiologists studying circadian rhythms with those studying developmental brain plasticity, Kobayashi notes. It could open inquiries into the role of circadian rhythm genes beyond the visual system, including brain regions that control cognition and social behaviors.. Specifically, the findings may have implications for disorders such as autism and schizophrenia. A number of genes associated with mental illness were expressed differently in the PV-cells of Clock-deficient versus control mice. The Hensch group and others have long proposed a link between neurodevelopmental disorders and timing defects in critical periods of brain plasticity. And finally, factors that influence circadian rhythms-sleep deprivation, seasonal changes limiting sunlight exposure, night shift work, etc.-have been linked to mood disorders.. By implicating circadian rhythm genes in the control of developmental brain plasticity, the new study may help bridge these ideas and suggests that ...
Hodžić A, Ristanović M, Zorn B, Tulić C, Maver A, Novaković I, Peterlin B. PLoS One. 2013;8(3):e59220. A case-control study was performed to determine the role of circadian genes in male infertility. The study consisted of 517 cases and 444 controls, all of which were of Slavic origin and recruited from three outpatient fertility centres. A chi-square test found…
The results of the present study demonstrate the novel finding that Per1 KO mice exhibit lower BP relative to WT mice, with significantly lower systolic and diastolic pressures. We reported previously that loss of Per1 reduced expression of αENaC and resulted in increased urinary sodium.6 A candidate gene approach was used to identify additional Per1 target genes involved in the regulation of sodium transport. We show that mRNA levels of the Na, K-ATPase effector Fyxd5 were reduced in Per1 knockdown cells. Furthermore, several negative effectors of ENaC activity, Cav-1, Ube2e3, and ET-1, were induced in response to Per1 knockdown. Importantly, we show for the first time that renal ET-1 peptide levels were elevated in Per1 KO mice. These results are consistent with a role for the circadian clock in the regulation of sodium homeostasis and BP.. Per1 KO animals exhibited an 18-mm Hg decrease in 24-hour mean arterial pressure relative to WT mice. These animals are on a 129/sv background, in which ...
... A place where the regulars of newgrounds can hang out that post during the late night hours. there will be things to do and they will try t...
Ebersol Says Conan Is Being Ousted Because Of His Disappointing Ratings NBC Sports & Olympics Chair Dick Ebersol Thursday said that the reason NBC is returning Jay Leno to the nets late-night roster after a short stint in prime time this season was a simple one: disappointing ratings for
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Viele Phänomene im Festkörper, wie z.B. die elektrische Leitfähigkeit hängen mit den Elektronen der Atome zusammen. Deshalb werden zuerst die Grundlagen von freien Elektronen im Potentialtopf, die...
In seltenen Fällen kann auch ein Antikörper gegen die C3-Konvertase des klassischen Weges-(C4bC2b) nachgewiesen werden. Ebenfalls sehr selten kann man Autoantikörper gegen C3 oder Nicht-C3Nef Autoantikörper gegen andere Bestandteile der C3-Konvertase nachweisen. Wegen der Seltenheit bleibt die Interpretation dieser Befunde in der Nephrologie problematisch.. ...
Umfassende Darstellung von medizinischen Laborparametern. Mehr als die H lfte aller Erkrankungen werden durch Laborparameter entdeckt oder im Verlauf kontrolliert.
Umfassende Darstellung von medizinischen Laborparametern. Mehr als die H lfte aller Erkrankungen werden durch Laborparameter entdeckt oder im Verlauf kontrolliert.
Umfassende Darstellung von medizinischen Laborparametern. Mehr als die H lfte aller Erkrankungen werden durch Laborparameter entdeckt oder im Verlauf kontrolliert.
TY - JOUR. T1 - Functional analysis of the circadian clock gene period by RNA interference in nymphal crickets Gryllus bimaculatus. AU - Moriyama, Yoshiyuki. AU - Sakamoto, Tomoaki. AU - Matsumoto, Akira. AU - Noji, Sumihare. AU - Tomioka, Kenji. PY - 2009/5. Y1 - 2009/5. N2 - The circadian clock gene period (Gryllus bimaculatus period, Gbper) plays a core role in circadian rhythm generation in adults of the cricket Gryllus bimaculatus. We examined the role of Gbper in nymphal crickets that show a diurnal rhythm rather than the nocturnal rhythm of the adults. As in the adult optic lobes, Gbper mRNA levels in the head of the third instar nymphs showed daily cycling in light-dark cycles with a peak at mid night, and the rhythm persisted in constant darkness. Injection of Gbper double-stranded RNA (dsRNA) into the abdomen of third instar nymphs knocked-down the mRNA levels to 25% of that in control animals. Most Gbper dsRNA injected nymphs lost their circadian locomotor activity rhythm, while ...
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Circadian rhythms, generated in the mouse suprachiasmatic nucleus (SCN), are synchronized to the environmental day-night changes by photic input. The activation of the extracellular signal-regulated kinases 1 and 2 (ERK1,2) and cAMP response element-binding protein (CREB)-mediated transcription play …
Circadian rhythms in physiology and behavior are observed in almost all phyla. Genetically encoded internal clocks generate such rhythms. Identification of gene products required for the generation and maintenance of endogenous circadian near 24-hr rhythms has led to a paradigm of multiple interlocked transcriptional/translational feedback loops as the basis for molecular circadian oscillators in all studied model systems. Protein phosphorylation plays an essential role, regulating the stability, activity and subcellular localization of proteins that constitute the biological clock. This study investigates the role of the protein kinase Doubletime, a Drosophila ortholog of casein kinase Is, in the fruit fly circadian clock. For the first time enzymatically active Doubletime protein is produced and direct phosphorylation of clock protein Period is demonstrated. Phosphorylation sites are identified and their functional significance is tested in a cell culture system. An in vivo analysis of a Period mutant
Drosophila has contributed an enormous wealth of experimental data and insight into the molecular dissection of the circadian clock. The negative feedback model was developed in the fly with PER (Siwicki et al. 1988; Hardin et al. 1990), and the fact that the murine clock is also built around the negative regulation of PER proteins further supports the generality of the higher eukaryote model (Shearman et al. 2000). One of the anchors for this model is that the per-encoded mRNAs and proteins cycle in pacemaker cells and that PER also enters the nucleus in a temporally regulated manner. Exactly what causes this temporal change in the relative abundance of PER between different cellular compartments is currently under debate (Nawathean and Rosbash 2004; Meyer et al. 2006), but the general observation that, in several insect orders, PER can be found to be exclusively cytoplasmic in its neuronal expression is inconsistent with its "dedicated" role as a circadian transcriptional regulator. One group ...
Further clues into the regulation of circadian clocks are the subject of two reports. In plants and insects, cryptochromes (CRYs) are activated by light, and in the fruit fly Drosophila, CRY blocks the negative feedback action of the PER-TIM complex. Griffin et al. show that CRY1 and CRY2 play a central role in the mammal clock, but in a light-independent fashion--they appear to regulate transcriptional cycling of Per1 by contacting both the activator and its feedback inhibitors. In Drosophila, three of the critical clock genes, period (per), timeless (tim), and Drosophila Clock (dClk), are expressed rhythmically. In their study of the cycling of dClk, Glossop et al. have found that the molecular clock in Drosophila is composed of two interlocked negative feedback loops--the per-tim loop, which is activated by the dCLK and CYCLE proteins and repressed by PER-TIM, and the dClk loop, in which these proteins exert the opposite effect.. Glossop, N.R.J., Lyons, L.C., and Hardin. P.E. (1999) ...
In collaboration with Hajime Tei, Ph.D., who successfully cloned a mammalian homologue of the Drosophila period gene, we developed a rodent model for monitoring real-time circadian gene expression rhythm by bioluminescence.. Using this technique, we discovered circadian clocks in mammalian peripheral organs. As a result, we view the mammalian circadian system as a multi-oscillator system, rather than a system controlled by one pacemaker structure in the SCN.. The discovery also allows biochemical analysis to be performed in abundant tissues such as the liver, which accelerated understanding of the molecular mechanisms of timekeeping. We realized that out-of-sync relationships among clocks in peripheral organs contribute to many human diseases. Every tissues internal circadian rhythm delicately controls the local physiology of that tissue; even small changes in that timing can result in malaise, such as metabolic syndrome and obesity.. ...
Subsets of brain neurons expressing the clock genes period (per) and timeless (tim) are involved in the generation of circadian behavioral rhythms. However, current knowledge of projection patterns of these neurons is limited to those immunoreactive to an antibody against a crustacean neuropeptide. …
Circadian clock gene expression in in vitro cultured CD4+ T cells and PER2::Luciferase CD4+ reporter T cells. Blood was sampled from 3 nutritious younger males
Drinking can have long-term harmful effects on the expression of circadian rhythm genes. This means alcohol abuse can have a drastic impact on sleep.
DSPS is where you fall asleep at an inconvenient time and can interfere with your work life and prospects. Sleep pattern out of control? Are you always tired? Get all the answers you need right here
Heard about brain science discoveries in the news?. Ever wonder how science creates the headlines?. Curious about how research happens at Columbia University Medical Center?. Heres your chance for a behind-the-scenes introduction to how neuroscience research works. Bring your family and friends to Late Night Science, a seminar series with lab tours by graduate students of Columbia University Neuroscience Outreach (CUNO).. Come join us for the next Late Night Science seminar, "How starving the brain promotes neurological disease" on September 15th at 6:15PM presented by Carlos Rueda, Ph.D. For more information, or to RSVP, click here: http://www.eventbrite.com/e/september-2016-late-night-science-tickets-25.... ...
When Nic Szeremeta had to figure out a way to make poker interesting on TV for Season 1 of Late Night Poker he knew exactly where to start: with the characters.
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Figure 3. The phase of circadian locomotor activity after release of LD22 desynchronized rats into DD. A, B, Representative double-plotted actograms of aligned-phase (A) and misaligned-phase (B) rats released into DD after a dark pulse (arrows), showing the eye-fitted onsets of the entrained locomotor onset (blue line), the dissociated locomotor bout (red line), and the fused, free-running locomotor bout (yellow line). C, D, Rayleigh phase plots showing the fused locomotor bout onsets for aligned-phase (gray squares) and misaligned-phase (black circles) animals, extrapolated to the day of control pulse. Onsets are referenced to the entrained bout onset and plotted on a 22 h timescale (C) or referenced to the dissociated bout onset, plotted on a 25 h timescale, which approximates the average period of the dissociated locomotor bout (D). ...
Thanks to new technology, scientists have a better understanding of what sections of the brain control certain behaviors. Like, say, a Borat impression. ...
Midnight Secret My Supertips, the Guerlain secret formula to help you recover from lack of sleep.|br/|A cocktail of effective ingredients helps to reduce th
Its a wonder that will always pop in our minds during tragedies, and also the million dollar question. Why Do Bad Things Happen to Good People? Im not going to pretend to know THE answer, because I dont think it really exists, but I will shed light on my opinion of it. I wont say…
If you are ever up late and near downtown then you should check out Jeffreys Wraps. They have the best chicken and steak wraps you can imagine. They
An distressing view Analytische Dynamik der Punkte und Starren Körper: Mit Einer Einführung in das of u2013 that will improve the other cholesterol in this treatment. The variants are made a cinematic and organized page of the Aesthetic rience, and assist intentional filters of what is derived about the risks and cells of beings and measures. I very are your security.
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... Klinisches W rterbuch von Otto Dornbl th. Definition und Bedeutung im historischen Lexikon der medizinischen Begriffe
Heroism for Harambe> is currently recruiting players such as yourself for late night raiding. We are a Heroic only guild that raid Tues/Wed from 7-10 Pacific (10-1 EST) on the Sargeras server (Alliance) and drop down to one night a week once the last boss is killed. We are largely former mythic raiders who wanted to step back from the grind but still see content. On off nights, we do mythic plus and play numerous other games ...
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When I was young, there was a local woman who was extremely unhappy with her husbands late night carousing. He would come home
Shadows of the evening - an essay on the importance of the daily cycle of night and day for plants and animals - as well as for mankind despite our modern 24 hour lifestyles. A reflective piece on a wider aspect of nature. Nov.99 ...
Post-traumatic stress disorder (PTSD) is associated with impaired conditioned fear extinction learning, a ventromedial prefrontal cortex (vmPFC)-dependent process. PTSD is also associated with dysregulation of vmPFC, circadian, and glucocorticoid hormone function. Rats have rhythmic clock gene expression in the vmPFC that requires appropriate diurnal circulatory patterns of corticosterone (CORT), suggesting the presence of CORT-entrained intrinsic circadian clock function within the PFC. We examined the role of vmPFC clock gene expression and its interaction with CORT profiles in regulation of auditory conditioned fear extinction learning. Extinction learning and recall were examined in male rats trained and tested either in the night (active phase) or in the day (inactive phase). Using a viral vector strategy, Per1 and Per2 clock gene expression were selectively knocked down within the vmPFC. Circulating CORT profiles were manipulated via adrenalectomy (ADX) ± diurnal and acute CORT ...
We have isolated the clock gene period (per) from the medfly Ceratitis capitata, one of the most economically important insect pest species. The overall pattern of conserved, non-conserved and functional domains that are observed within dipteran and lepidopteran per orthologues is preserved within the coding sequence. Expression analysis from fly heads revealed a daily oscillation in per mRNA in both light : dark cycles and in constant darkness. However PER protein levels from head extracts did not show any significant evidence for cycling in either of these two conditions. When the Ceratitis per transgene under the control of the Drosophila per promoter and 3UTR was introduced into Drosophila per -null mutant hosts, the transformants revealed a low level of rescue of behavioural rhythmicity. Nevertheless, the behaviour of the rhythmic transformants showed some similarities to that of ceratitis, suggesting that Ceratitis per carries species-specific information that can evidently affect the ...
Purpose: : Circadian rhythms are driven by a central clock (suprachiasmatic nucleus, SCN) and peripheral clocks (tissues) and determined by expression of "clock genes". Diabetic retinopathy (DR) is associated with endothelial precursor cell (EPC) dysfunction. We asked whether DR is associated with changes in clock genes expression within the retina, bone marrow (BM) and peripheral blood EPCs and whether this could influence EPC release from the BM and thus the ability of EPC to repair the vasodegenerative phase of DR. Methods: : Type 2 diabetic (n=3) rats with 4 months duration of disease and age matched controls (n=5) were placed in standard LD conditions for two weeks prior to sacrifice. With a 24-hr period divided into a 12-hr activity phase and a 12-hr rest phase. In nocturnal animals, such as rats, Zeitgeber time (ZT) 12 is at the beginning of the activity phase (dark) and ZT 0 (light) is at the start of the rest phase. At peak release of EPC at (ZT) 4, animals were sacrificed and their ...
Need to know more about Delayed Sleep Phase Syndrome? Find expert research & treatment advice from the American Sleep Association - Official Site.
article{3062551, abstract = {Previously, we identified HISTONE MONOUBIQUITINATION1 (HUB1) as an unconventional ubiquitin E3 ligase that is not involved in protein degradation but in the histone H2B modification that is implicated in transcriptional activation in plants. HUB1-mediated regulation of gene expression played a role in periodic and inducible processes such as the cell cycle, dormancy, flowering time and defense responses. Here, we determined the effects of the hub1-1 mutation on expression of a set of diurnally induced circadian clock genes identified from a comparative microarray analysis between the hub1-1 mutant and an HUB1 over-expression line. The hub1-1 mutation reduced the amplitudes of a number of induced clock gene expression peaks, as well as the HUB1-mediated histone H2BUb and H3K4Me3 marks associated with the coding regions, suggesting a role for HUB1 in facilitating transcriptional elongation in plants. Furthermore, double mutants between hub1-1 and elongata (elo) showed ...