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Label: Molecular Recordings - MRCD 02-2 • Format: CD Compilation, Enhanced • Country: UK • Genre: Electronic • Style: Techno

Authors: Johannes Thome. Published on: 16 May Published on: 4 March Autism spectrum disorder ASD is heritable and neurodevelopmental with unknown causes. The serotonergic and oxytocinergic systems are of interest in autism for several reasons: i Both systems are implicated Published on: 24 January The neurotrophins brain-derived neurotrophic factor BDNF and neurotrophic factor 3 NT3 could play a role in addictive behavior.

Interactions between BDNF and dopamine transmission influence the alcohol int Citation: Journal of Molecular Psychiatry 1 Published on: 2 December The dopamine DA hypothesis of schizophrenia proposes the mental illness is caused by excessive transmission of dopamine in selected brain regions. Multiple lines of evidence, including blockage of dopamine r Published on: 4 November The goal of this review is to integrate - in its two parts - the considerable amount of information that has accumulated during these recent years over the morphology, biology Various - Bio Molecular Rhythms Volume Two (CD) functions of astrocytes - fir Published on: 24 October We explored the role of Nucleus accumbens Nac as a target fo Published on: 23 October Autism Spectrum Disorders ASD are group of developmental disabilities with a complex neurobiological basis including putative changes in the immune system.

They are characterized by pervasive qualitative abn Published on: 17 September Depression is a prevalent neuropsychiatric disorder that affects an estimated million people worldwide. Currently available treatments for depression are lacking in both speed of onset and efficacy. Ageing is associated with changes in the function of various organ systems. Changes in the cardiovascular system affect both directly and indirectly the function in a variety of organs, including the brain, wi Published on: 23 August Alcohol-induced damages such as brain atrophy and fatty liver are closely related to a disturbed lipid metabolism.

In animal models, a linkage between chronic alcohol consumption and changes in fatty acid FA In the last years, physiological aging became a general concept that includes all the changes that occur in organism with old age.

It is obvious now, that in developing and developed countries, new health prob Published on: 17 July Alcohol dependence is a severe and common disorder associated with high morbidity and mortality rates. Genetic as well as environmental factors are known to modulate susceptibility to alcohol dependence. Published on: 11 July Content type: Erratum. Published on: 10 June The original article was published in Journal of Molecular Psychiatry 1 The amygdala is a structure of the temporal lobe thought to be involved in assigning emotional significance to environmental information and triggering adapted physiological, behavioral and affective responses Published on: 5 June The search for molecules that can act as potential biomarkers is increasing in the scientific community, including in the field of psychiatry.

The field of proteomics is evolving and its indispensability for i Disruption of circadian rhythms is associated with several deleterious health consequences and cognitive impairment. It is estimated that as many as one in five workers are exposed to this risk factor due to e Published on: 29 May Furthermore, we studied diurnally expression patterns of genes such as vasopressin receptors, urea transporters, and water channels in mice.

Finally, we examined day-night variations of cortico-medullary osmotic pressure gradient in Bmal1 deficient mouse kidneys. We found strong signals in the medulla, along with renal tubule.

PERLuc activity was also observed in the cortex and small spotted signals comparable to glomerulus were found Fig. Quantitative analysis by setting regions of interests ROIs in the IM, OM and cortex revealed bioluminescence in these areas clearly circadian oscillated lasting at least three days Fig. Localization of PERLuc activity in kidney.

A bright field image left and a luminescence image right are displayed. We set 0hr when we started observations. Set ROIs are shown in d, Various - Bio Molecular Rhythms Volume Two (CD). Circadian rhythmic signal intensities were observed in the cortex, OM, and IM e. Next, we collected rat kidneys at Zeitgeber time ZT 0, 4, 8, 12, 16, and 20 where ZT12 is the time of light off. We measured electrolytes and urea concentrations, and calculated osmotic pressure in the IM and cortex.

This suggests that cortico-medullary osmotic pressure gradient changes diurnally depending on osmotic pressure rhythm in the IM. Diurnal variations of electrolytes, urea concentrations, and osmotic pressure in rat kidney. From left to right, diurnal variations of sodium, potassium, chloride, and urea concentrations are shown.

White and black rectangles in graphs indicate the light phase and the dark phase, respectively. Clock genes and genes contributing high osmotic pressure gradient and water re-absorption in mouse kidney. Aqp2Aqp3and Aqp4 are expressed in the collecting ducts CD orange. Aqp4 expression was hardly detected in the cortex Fig. To analyze the necessity of molecular clock in diurnal variations of osmotic pressure gradient, we studied osmotic pressure, electrolytes and urea concentrations in systemic Bmal1 deficient mice which completely lack a functional clock As shown in Fig.

White and black rectangles in graphs indicate light phase and dark phase, respectively. In wild type mice, osmotic pressure in the IM at ZT16 was 1. These results are similar to day-night variations in rat kidneys Fig. Na and urea concentrations also showed similar patterns in Bmal1 deficient mice Fig.

Any day-night variations in osmotic pressure and electrolytes except for K in the cortex was not observed in either wild type or Bma11 deficient mice Fig. Day-night variations of osmotic pressure, electrolytes, and urea concentrations in wild type and Bmal1 deficient mouse kidney. From left to right, day-night difference of sodium, potassium, chloride, and urea concentrations are shown. We used pooled IM and cortex samples from three mice as one sample for measurement and performed four independent experiments.

Both a and GFR reflecting in b are larger at night As b is nearly a hundred-times larger than a 50circadian variation of b is mainly reflected in the circadian variation of c. Therefore, c active phase is higher than c rest phase. White and black rectangles in schema indicate the light phase and the dark phase, respectively.

In this study, we revealed the tissue-autonomous circadian clock oscillation in cultured kidneys using bioluminescence macroscopic imaging devices. Our finding that strong and robust circadian oscillation of the bioluminescence in the medulla highlights molecular clock functions in medullas, including a thin descending and ascending limb of loop of Henle and collecting duct Fig.

Local clock functions in the kidney have been approached by transcriptomic study using laser micro-dissected samples or physiological analysis using several kinds of conditional KO mice 35 However, most studies have analyzed molecular clocks on the whole kidney level or cortex, whereas few studies have focused on the molecular clock in functions of the medulla 2628 Various - Bio Molecular Rhythms Volume Two (CD), In this study, by performing real-time bioluminescence imaging analysis at the organ level, we succeeded not only in showing regional tissue-autonomous molecular clocks oscillating in the kidney, but also to highlight local clock functions in the IM.

Urine volume displays a circadian rhythm, but the whole mechanism remains unclear. Micturition volume is influenced by bladder capacity which is under circadian control via Cox43 Urine production is depended on several parameters including blood pressure, the renal blood flows RBFthe glomerular filtration rate GFRblood vasopressin levels, the cortico-medullary osmotic pressures gradient 4 Blood pressure exhibits a robust circadian rhythm peaking at active phase 38and urine volume also has circadian rhythm peaking at active phase 2021 Moreover, both Bmal1 deficient mice and Cry1Cry2 double knock out mice Cry -null mice that abolish clock gene regulation in whole body completely lose the circadian variation in blood pressure 3839and Cry -null mice also lose urination rhythm These results suggest that blood pressure rhythmicity may affect the urine volume rhythmicity.

Cortico-medullary osmotic pressure gradient also affect urine volume via water reabsorption. In this study, we revealed, for the first time, that the osmotic pressure in the IM and the osmotic pressure gradient is higher at night than those during the day in rats Fig. Supporting this, we observed similar results in mice Fig.

Our data indicate that diurnal rhythms of cortico-medullary osmotic pressure gradients also may contribute to urine volume rhythmicity. Furthermore, day-night variations of osmotic pressure in the IM and the osmotic pressure gradient was disrupted in Bmal1 deficient mice Fig. Together with strong circadian clock oscillation in the IM observed by macro-imaging analysis, these data suggest that the medullary clock plays an important role in generating cortico-medullary osmotic pressure gradient rhythm.

Urea is considered a key player for generating high osmotic pressure in the IM In this study, we found urea concentrations in the IM showed diurnal rhythm peaking at night-time Fig. By facilitating urea recycling between the inner medulla collecting duct and thin descending limb segments, UT-A2 is thought to support for maintaining hypertonic medulla that provides the driving force for water re-absorption from the collecting ducts In humans, some studies showed that vasopressin concentrations increase at night rest phase and it results in urine volume decrease and urine concentration increase at rest phase The circadian rhythm of blood vasopressin levels is under discussion.

Although some studies reported diurnal rhythm of serum vasopressin level peaking at late resting phases in humans and rats 45Various - Bio Molecular Rhythms Volume Two (CD), 4647others observed no rhythmicity 48 This inconsistency probably occurred from low concentrations of vasopressin levels Noticeably, vasopressin receptors, V1aR and V2Rare revealed to show circadian rhythm We also observed the same results Fig.

As V2R mediates the anti-diuretic effect of vasopressin in the kidney, this suggests that circadian rhythmic functions via vasopressin signalling may be achieved by rhythmic expression of vasopressin receptors. Although water re-absorption is mainly regulated in the IM, about two thirds of re-absorption occurs in proximal tubule which are located in the cortex In the cortex, though amplitude was low, we found the rhythmic expression of Aqp1 which plays an important role in water re-absorption there.

Gathering all data observed in this study including osmotic pressures and urea concentrations in the IM, water re-absorption rate is suggested to be high at night active phase and low during the day rest phase. Diurnal rhythm of water re-absorption peaking at the active phase is also suggested from diurnal rhythms of urine volume and GFR Since the volume of primitive urine is nearly a hundred-times larger than excreted urine volume 50it is consistent with the in-phase circadian rhythms of primitive urine and water re-absorption as shown in Fig.

The mechanism of urine concentration is Various - Bio Molecular Rhythms Volume Two (CD) regulated because even slight changes in primitive urine re-absorption can lead significant effects on body fluid homeostasis. The circadian clock is likely to regulate osmotic Various - Bio Molecular Rhythms Volume Two (CD) gradient actively for dealing with increasing water re-absorption at active phases effectively. In conclusion, we identified robust regional of circadian clock oscillation in the medulla of kidneys by real-time bioluminescence imaging using macroscopic observation devices, which enabled us to evaluate the circadian clock rhythmicity in the whole kidney level.

This approach highlights importance of IM circadian clock. We found that osmotic pressure in the IM showed diurnal rhythms, but not in the cortex. We found that osmotic pressure gradient was high at night active phase but not in Bmal1 deficient mice.

These findings suggest that the circadian clock affected the generation of cortico-medullary osmotic pressure gradient rhythm via, at least in part, molecular rhythms of urea transporters, water channels, and vasopressin receptors. I mice 11 and Bmal1 deficient mice were kept under hour light and hour dark LD conditions in our facility Genotyping of Bmal1 deficient mice was performed using PCR Food and water were available ad libitum.

Rat kidneys were processed as Schimidt-Nielsen et al. Kidneys were dissected, and white color region were collected as IM. To collect the cortex, arcuate artery, arcuate vein, and the color difference between the cortex and OM were used as landmarks. The osmotic pressure was estimated as the sum of the urea concentration and two times the sum of Na and K concentration. Similar to rats, mouse kidneys were divided into IM and Cortex, pooled into plastic tubes separately, and dried as described above.

Since mouse kidneys are smaller than rat, the kidneys collecting from three mice were pooled as one sample at each time point and we performed four independent studies. Gene expression levels were calculated from relative standard curves and normalized to 18s ribosomal RNA. To compare two groups Bmal1 deficient mice and their wild type littermates in Fig. Lowrey, P. Genetics of circadian rhythms in Mammalian model organisms. Advances in genetics.

Bass, J. Circadian topology of metabolism. Masri, S. The circadian clock transcriptional complex: metabolic feedback intersects with epigenetic control. Annals of the New York Academy of Sciences. Firsov, D. Circadian regulation of renal function. Kidney international. Hastings, M. A clockwork web: circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci. Schibler, U. In this study, we found urea concentrations in the IM showed diurnal rhythm peaking at night-time Fig.

By facilitating urea recycling between the inner medulla collecting duct and thin descending limb segments, UT-A2 is thought to support for maintaining hypertonic medulla that provides the driving force for water re-absorption from the collecting ducts In humans, some studies showed that vasopressin concentrations increase at night rest phase and it results in urine volume decrease and urine concentration increase at rest phase The circadian rhythm of blood vasopressin levels is under discussion.

Although some studies reported diurnal rhythm of serum vasopressin level peaking at late resting phases in humans and rats 45 — 47others observed no rhythmicity 48 This inconsistency probably occurred from low concentrations of vasopressin levels Noticeably, vasopressin receptors, V1aR and V2Rare revealed to show circadian rhythm We also observed the same results Fig.

As V2R mediates the anti-diuretic effect of vasopressin in the kidney, this suggests that circadian rhythmic functions via vasopressin signalling may be achieved by rhythmic expression of vasopressin receptors. Although water re-absorption is mainly regulated in the IM, about two thirds of re-absorption occurs in proximal tubule which are located in the cortex In the cortex, though amplitude was low, we found the rhythmic expression of Aqp1 which plays an important role in water re-absorption there.

Gathering all data observed in this study including osmotic pressures and urea concentrations in the IM, water re-absorption rate is suggested to be high at night active phase and low during the day rest phase. Diurnal rhythm of water re-absorption peaking at the active phase is also suggested from diurnal rhythms of urine volume and GFR Since the volume of primitive urine is nearly a hundred-times larger than excreted urine volume 50it is consistent with the in-phase circadian rhythms of primitive urine and water re-absorption as shown in Fig.

The mechanism of urine concentration is tightly regulated because even slight changes in primitive urine re-absorption can lead significant effects on body fluid homeostasis. The circadian clock is likely to regulate osmotic pressure gradient actively for dealing with increasing water re-absorption at active phases effectively.

In conclusion, we identified robust regional of circadian clock oscillation in the medulla of kidneys by real-time bioluminescence imaging using macroscopic observation devices, which enabled us to evaluate the circadian clock rhythmicity in the whole kidney level.

This approach highlights importance of IM circadian clock. We found that osmotic pressure in the IM showed diurnal rhythms, but not in the cortex. We found that osmotic pressure gradient was high at night active phase but not in Bmal1 deficient mice. These findings suggest that the circadian clock affected the generation of cortico-medullary osmotic pressure gradient rhythm via, at least in part, molecular rhythms of urea transporters, water channels, and vasopressin receptors.

I mice 11 and Bmal1 deficient mice were kept under hour light and hour dark LD conditions in our facility Genotyping of Bmal1 deficient mice was performed using PCR Food and water were available ad libitum. Rat kidneys were processed as Schimidt-Nielsen et al.

Kidneys were dissected, and white color region were collected as IM. To collect the cortex, arcuate artery, arcuate vein, and the color difference between the cortex and OM were used as landmarks. The osmotic pressure was estimated as the sum of the urea concentration and two times the sum of Na and K concentration.

Similar to rats, mouse kidneys were divided into IM and Cortex, pooled into plastic tubes separately, and dried as described above. Since mouse kidneys are smaller than rat, the kidneys collecting from three mice were pooled as one sample at each time point and we performed four independent studies.

Gene expression levels were calculated from relative standard curves and normalized to 18s ribosomal RNA. To compare two groups Bmal1 deficient mice and their wild type littermates in Fig. We thank Dr. Yoko Hatta-Ohashi Olympus for setting up the bioluminescence macroscopy. Study conduct: M. Data analysis: M. Data interpretation: M. Drafting manuscript: M. All authors approved final version of manuscript. Electronic supplementary material.

Supplementary information accompanies this paper at doi Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. National Center for Biotechnology InformationU. Sci Rep. Published online Aug 4. Author information Article notes Copyright and License information Disclaimer. Kazuhiro Yagita, Email: pj. Corresponding author. Received Mar 23; Accepted Jun This article has been cited by other articles in PMC.

Supplementary Information. Abstract Circadian clocks in mammals function in most organs and tissues throughout the body. Open in a separate window. Figure 1.

Diurnal rhythms of the osmotic pressure and osmotic pressure gradient Next, we collected rat kidneys at Zeitgeber time ZT 0, 4, 8, 12, 16, and 20 where ZT12 is the time of light off. Figure 2. Diurnal rhythms of gene expressions in the IM and cortex of the kidney Then, we analyzed diurnal expression patterns of genes contributing high osmotic pressure in the IM and re-absorption water in the IM and cortex of mouse kidneys by quantitative PCR qPCR analysis Fig. Figure 3.

Impaired inner medullary rhythms in Bmal1 deficient mice To analyze the necessity of molecular clock in diurnal variations of osmotic pressure gradient, we studied osmotic pressure, electrolytes and urea concentrations in systemic Bmal1 deficient mice which completely lack a functional clock Figure 4. Figure 5. Discussion In this study, we revealed the tissue-autonomous circadian clock oscillation in cultured kidneys using bioluminescence macroscopic imaging devices.

Measurement of osmotic pressure Rat kidneys were processed as Schimidt-Nielsen et al. Electronic supplementary material Supplementary Video S1 K, avi.

Supplementary Information K, pdf. Acknowledgements We thank Dr. Notes Competing Interests The authors declare that they have no competing interests.

Footnotes Electronic supplementary material Supplementary information accompanies this paper at doi References 1. Genetics of circadian rhythms in Mammalian model organisms. Advances in genetics. Bass J. Circadian topology of metabolism. The circadian clock transcriptional complex: metabolic feedback intersects with epigenetic control. Annals of the New York Academy of Sciences. Firsov D, Bonny O. Circadian regulation of renal function. Kidney international.

A clockwork web: circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci. Schibler U, Naef F. Cellular oscillators: rhythmic gene expression and metabolism. Current opinion in cell biology.


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    Susan S. Golden, 1 Masahiro Ishiura, 2 Carl Hirschie Johnson, 3 and Takao Kondo 2 1 Department of Biology, Texas A&M University, College Station, Texas, 2 Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya, Japan. 3 Department of Biology, Vanderbilt University, Nashville, Tennessee

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