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Three genes essential for cells to tell time -- ScienceDaily

"Many researchers in this field have long suspected oxidative stress and circadian rhythms are somehow connected because of the cycles of photosynthesis and DNA replication we see even in ancient organisms; photosynthesis requires sunlight and creates free radicals that could damage DNA, so cells postpone DNA replication and cell division until nighttime when photosynthesis has stopped. We are very excited about our results because we can approach the origin of the circadian clock by connecting oxidative stress and circadian regulation through the Ask genes," said Fukada.

Another way morning exercise resets your circadian rhythm?

In flies, temperature could be sensed directly by neurons in the brain or via nerve impulses from sensory organs in the body. To distinguish between the two, the investigators genetically manipulated or physically removed the sensory organs and found that the DN1p neurons no longer responded to changes in temperature. This meant that the clock interprets temperature signals from the body rather than sensing temperature changes directly. The circadian clock of larger animals and humans is also sensitive to changes in temperature, and because of their larger size, would require input from external sensory organs. The fact that, despite its small size, the fly clock also relies on temperature sensors outside the brain suggests that the findings of this study could have broad implications in the control of sleep in humans.

Our circadian clock sets the rhythm for our cells’ powerhouses -- ScienceDaily

Countless genetically controlled clocks tick inside different parts of our bodies, such as the liver, kidneys and heart. Among other things, they initiate many metabolic processes, ensuring that these occur at the optimal time of day. Mitochondria -- small organelles that exist in almost all our cells and supply them with energy -- play an important role in these cellular processes. Until now, it was unclear how exactly the 24-hour circadian rhythm regulated energy metabolism. Fission protein sets the rhythm In most cells, mitochondria connect in a constantly changing network that can adapt to various conditions. Mitochondria can thus fuse together and then divide again. Disruption of this fission-fusion dynamic can lead to health problems. Researchers have now investigated exactly how the mitochondrial network interacts with our internal biological clock by using a combination of in vitro models and clock-deficient mice or mice with impaired mitochondrial fission. Their results show that the mitochondrial fission-fusion cycle is controlled by the fission protein Drp1, which is in turn synchronized by an internal biological clock. This rhythm is integral to determining when and how much energy the mitochondria can supply. "The time of day determines the design of the mitochondrial network, and this, in turn, influences the cells' energy capacity," explains study leader Professor Anne Eckert from the University of Basel's Transfaculty Research Platform Molecular and Cognitive Neurosciences MCN.

Recap of sunlight with links

Although medical curiosity about the salubrious benefits of sunlight exposure can be traced to antiquity [1,2], contemporary clinical interest was ignited by the 20th-century discovery of a direct link between light exposure and circadian melatonin production [3,4]. An obvious initial candidate for bright light therapy (LT) was seasonal affective disorder [5] – a form of depressive illness typically triggered by light deprivation during the short, cold days of winter – and the intervention has proven to be efficacious across a large number of randomized controlled trials [6-8]. In fact, the efficacy of LT has now been supported across a range of other mood disorders, including non-seasonal depression [9,10,6], bipolar disorder [11,12], antepartum and postpartum depression [13,14], and premenstrual dysphoric disorder [15,16]. Light therapy (LT) has also been successfully applied to the treatment of sleep disorders [17-20], as well as circadian phase sleep disorders associated with jet lag [21,22] and shift work [23,24]. More recently, LT has shown promise as an intervention for obsessive-compulsive symptoms [25], behavioral disturbances and functioning in dementia and Alzheimer’s disease [26,27], primary and secondary features of Parkinson’s disease [28], attention deficit hyperactivity disorder [29], seasonal variations in eating disturbances associated with bulimia nervosa [30,31], and some symptoms of chronic anorexia [32].

The link between circadian rhythms and aging: Gene associated with longevity also regulates the body's circadian clock -- ScienceDaily

Last year, Guarente found that a robust circadian period correlated with longer lifespan in mice. That got him wondering what role SIRT1, which has been shown to prolong lifespan in many animals, might play in that phenomenon. SIRT1, which Guarente first linked with aging more than 15 years ago, is a master regulator of cell responses to stress, coordinating a variety of hormone networks, proteins and genes to help keep cells alive and healthy.

Visualizing assemblies of the proteins that direct cyanobacterial circadian rhythms

KaiB, though, flips between two different shapes, and is only active when it's in an unstable shape—a situation that until now made crystallization impossible. "We mutated KaiB so that it stayed in its active shape, and when we added KaiA and KaiC they arranged themselves around it as they do at night," LiWang said. "We found the secret sauce that allows us to figure out how the springs and gears go together." They were amazed that they obtained crystals within a day of combining the proteins. They also solved an NMR structure of a complex between the active form of KaiB and the domain of a protein (CikA) that transmits signals to regulate gene expression in cyanobacteria. "It's really remarkable that the cyanobacterial clock is so dependent on this rare state of KaiB," Partch said. "The mechanistic information we're getting out of these structures is allowing us to piece together how the clock manages to keep 24-hour time. We're now looking for similar clues in other circadian timekeeping systems, including our own."

Timing is everything, to our genes -- ScienceDaily

Using RNA sequencing, the research team tracked gene expression in dozens of different non-human primate tissues every 2 hours for 24 hours. The team found that each tissue contained genes that were expressed at different levels based on the time of day. However, the number of these "rhythmic" genes varied by tissue type, from around 200 in pineal, mesenteric lymph nodes, bone marrow and other tissues to more than 3,000 in prefrontal cortex, thyroid, gluteal muscle and others. In addition, genes that were expressed most often tended to show more rhythmicity, or variability by time. Of the 25,000 genes in the primate genome, nearly 11,000 were expressed in all tissues. Of those (which mostly govern routine cellular functions, such as DNA repair and energy metabolism), 96.6 percent were particularly rhythmic in at least one tissue, varying drastically by when they were sampled.

Insomnia and depression: Japanese hospital workers questionnaire survey : Open Medicine

Chronic insomnia is the one of the factors influencing the development of mental illness. In this survey, we tried to clarify the relationship between chronic insomnia and various factors. Although there is no certainty about other possible independent variables, multiple regression analyses suggested that chronic insomnia is an important factor for depression. Koyama et al. found that subjects who suffered from severe sleeping disorders, not just during depression, tended to have decreased blood flow in the frontal lobe of the brain [2]. When SIGH-D was used to evaluate sleeping disorders, an IS of 3 or higher showed that its severity and the reduced blood flow in the frontal lobe are significantly correlated. Based on this biological finding, preliminary research was conducted with 108 working participants, which included healthy participants and patients with mild to moderate depressive episodes. The result showed that the IS was significantly correlated with the severity of depression, subjective fatigue, sadness, and suicidal thoughts. Thus, an IS evaluation has the possibility of identifying depression based on a questionnaire survey related to direct mood changes [3]. There have been robust findings concerning the biology underlying the close relationship between sleep disorders and depression. For example, Buckley has found that a protracted sleep disorder, not depression, induces hyperactivity of the HPA (hypothalamic-pituitary-adrenal axis) system [14]. Furthermore, exposure to extreme stress causes the excessive secretion of corticotropin releasing hormone (CRH) —a cerebral mechanism for stress adaptation. This release of CRH inhibits the activities of the serotonin pathway in the nervous system that extends from the dorsal raphe nucleus to the prefrontal area via the gamma-aminobutyric acid (GABA) system [15]. It is also known that CRH has a stimulant effect [14]. Therefore, it is inferred that a substantive lack of sleep will lead to a sustained activation of the HPA system once again, thus establishing a vicious cycle. On the other hand, the decline in frontal lobe function due to depression has been established by several earlier studies, including those that used functional brain imaging [15,16,17,18]. The protraction of a sleep disorder activating the HPA system and inhibiting the serotonin nervous system in the frontal lobe is believed to elicit a clinical condition similar to depression. Furthermore, the finding that the hyperactivity of the HPA system increases cortisol secretion, which inhibits the HPA system and damages hippocampal cells, further strengthens the suggested relationship between sleep disorders and depression. This biological finding strengthens the theory that a lack of sleep due to insomnia, exposure to stress, and overwork, leads to depression because of the accumulation of mental fatigue.

Clock protein controls daily cycle of gene expression by regulating chromosome loops: New understanding of Rev-erb's role has implications for metabolic disorders, cardiovascular disease, and cancer -- ScienceDaily

Human physiology works on a 24-hour cycle of gene expression (when the chromosome coding region is translated by RNA and then transcribed to make protein) and is controlled by the body's molecular clock. Core clock proteins activate or repress protein complexes that physically loop one part of a chromosome to become adjacent to a distant part of the same chromosome. The Penn team showed that daily oscillations of Rev-erb control gene expression in the mouse liver via interactions between on-and-off regions on the same chromosome. Previous work from the team demonstrated that by 5 p.m., Rev-erb increases to its highest concentration in mouse liver, where it turns off certain genes and therefore protein transcription. But as the day turns to night, its concentration steadily decreases and nearly vanishes from the liver by 5 a.m.

irregular sleep screws you

the researchers were able to assess the timing of circadian rhythms. On average, melatonin was released 2.6 hours later in students with the most irregular sleep patterns, compared with students with more regular sleep patterns.

Female night shift workers may have increased risk of common cancers -- ScienceDaily

Overall, long-term night shift work among women increased the risk of cancer by 19 percent. When analyzing specific cancers, the researchers found that this population had an increased risk of skin (41 percent), breast (32 percent), and gastrointestinal cancer (18 percent) compared with women who did not perform long-term night shift work. After stratifying the participants by location, Ma found that an increased risk of breast cancer was only found among female night shift workers in North America and Europe. "We were surprised to see the association

Time matters: Does our biological clock keep cancer at bay? -- ScienceDaily

Relógio, whose surname in Portuguese means "clock," says: "Based on our results, it seems to us that the clock is likely to act as a tumour suppressor, and that it is of advantage for cancer cells to circumvent circadian control. One cannot stop wondering whether disrupted circadian timing should be included as a next potential hallmark of cancer."

Outdoor light at night linked with increased breast cancer risk in women | News | Harvard T.H. Chan School of Public Health

Women exposed to the highest levels of outdoor light at night—those in the top fifth—had an estimated 14% increased risk of breast cancer during the study period, as compared with women in the bottom fifth of exposure, the researchers found. As levels of outdoor light at night increased, so did breast cancer rates.

Our muscles measure the time of day -- ScienceDaily

Biochemistry Department of the Faculty of Sciences, UNIGE, who codirected the study in Geneva with colleague Charna Dibner, from the Department of Internal Medicine Specialties, from the Faculty of Medicine, UNIGE. "As the combination of lipids varied substantially from one individual to another, we needed further evidence to corroborate these findings," he explains. In a second step, the researchers switched to an in-vitro experiment. They cultivated human muscle cells and artificially synchronised them in the absence of a master clock, using a signal molecule normally secreted in the body. The researchers observed a periodic variation in the cell's lipid composition, similar to what they noticed in human subjects. But when they disrupted the clock mechanism by inhibiting the responsible genes, the periodically changing variations in the lipids were mostly lost.

Is ADHD really a sleep problem? -- ScienceDaily

"There is extensive research showing that people with ADHD also tend to exhibit sleep problems. What we are doing here is taking this association to the next logical step: pulling all the work together leads us to say that, based on existing evidence, it looks very much like ADHD and circadian problems are intertwined in the majority of patients. We believe this because the day and night rhythm is disturbed, the timing of several physical processes is disturbed, not only of sleep, but also of temperature, movement patterns, timing of meals, and so on. If you review the evidence, it looks more and more like ADHD and sleeplessness are 2 sides of the same physiological and mental coin."

How circadian clocks communicate with each other -- ScienceDaily

The Würzburg researchers found their master and slave theory confirmed by the work of their Chilean colleagues. The researchers in Chile had conducted a number of experiments in which they had artificially slowed down the circadian clocks of Drosophila in various combinations and observed the impact on the hatching behaviour. The results: When both clocks run more slowly, the "hatching rhythm" increases from normally 24 hours to over 27. A similar effect is observed when the peripheral clock continues to run at regular speed and the central clock is slowed down. Vice versa, however -- i.e. normal working central clock and slowed down peripheral clock -- the hatching behaviour remains unchanged at a 24-hour interval. "This is the first comprehensive experimental description of a pathway that links circadian clocks and it shows that the coupled-oscillator model is actually true in certain cases," says Christian Wegener. But he admits that science is still a long way from understanding the exact interactions of the circadian clocks. After all, the recent findings illustrate that the diverse mechanisms are heavily interwoven and provided with feedback loops. So Wegener is certain that "it is not going to be easy."

The Benefits of Exercising Before Breakfast - The New York Times

At the end, the nonexercising group was, to no one’s surprise, super-sized, having packed on an average of more than six pounds. They had also developed insulin resistance — their muscles were no longer responding well to insulin and weren’t pulling sugar (or, more technically, glucose) out of the bloodstream efficiently — and they had begun storing extra fat within and between their muscle cells. Both insulin resistance and fat-marbled muscles are metabolically unhealthy conditions that can be precursors of diabetes. The men who ate breakfast before exercising gained weight, too, although only about half as much as the control group. Like those sedentary big eaters, however, they had become more insulin-resistant and were storing a greater amount of fat in their muscles. Only the group that exercised before breakfast gained almost no weight and showed no signs of insulin resistance. They also burned the fat they were taking in more efficiently. “Our current data,” the study’s authors wrote, “indicate that exercise training in the fasted state is more effective than exercise in the carbohydrate-fed state to stimulate glucose tolerance despite a hypercaloric high-fat diet.”

Why Everything We Know About Salt May Be Wrong - The New York Times

Their urine volumes went up and down in a seven-day cycle. That contradicted all he’d been taught in medical school: There should be no such temporal cycle. In 1994, the Russian space program decided to do a 135-day simulation of life on the Mir space station. Dr. Titze arranged to go to Russia to study urine patterns among the crew members and how these were affected by salt in the diet. A striking finding emerged: a 28-day rhythm in the amount of sodium the cosmonauts’ bodies retained that was not linked to the amount of urine they produced. And the sodium rhythms were much more pronounced than the urine patterns.

Circadian meta rhythm needed for consciouness?

of Surrey and the University of Salzburg, Austria, examined circadian body temperature variations of 18 patients suffering from severe brain injuries and the potential link to consciousness. Circadian rhythms are an approximate 24-hour cycle governed by the body's internal clock and they determine a number of physiological processes in the body including core body temperature, which fluctuates throughout the day. To assess the body temperature of patients, researchers used four external skin sensors to monitor the circadian rhythm, which was found to range between 23.5 hours and 26.3 hours. The level of consciousness of each patient was evaluated through the Coma Recovery Scale-Revised, which among others measures responsiveness to sound or a patient's ability to spontaneously open eyes without or only with stimulation by the examiner. Researchers discovered that patients who scored better on the Coma Recovery Scale-Revised, especially, those patients with a stronger arousal had body temperature patterns that were more closely aligned with a healthy 24-hour rhythm. This finding demonstrates a newly discovered relationship between circadian body temperature variation and the level of consciousness of a patient with severe brain damage. This finding suggests that patient's consciousness levels should be assessed during time windows when their circadian rhythm predicts them to be more responsive. The effects of bright light stimulation on patients with severe brain injuries was also investigated during this study. To measure its effectiveness, eight patients received bright light stimulation, three times per day for one hour over the course of one week. After one week, improvements were found in the level of consciousness of two patients, whose condition improved from vegetative state/unresponsive wakefulness to a minimally conscious state. Interestingly, in these two patients, a shift in their circadian body temperature, closer to a healthy 24-hour rhythm was also recorded. Co-investigator of the paper Dr Nayantara Santhi from the Surrey Sleep Research Centre, University of Surrey, said: "Prior to our study little was known about the circadian rhythms of patients with brain injuries. What we have learnt is that the circadian body temperature holds vital clues to the state of consciousness of patients which could potentially enable doctors to tailor medical treatment more effectively. "Circadian rhythms hold the secret to the workings of the body and we will be looking further into this in future research."

Cellular jetlag seems to favor the development of diabetes -- ScienceDaily

studied pancreatic ɑ- and β- cells that are in charge of the production of insulin and glucagon, two hormones that regulate glucose levels in the blood. They discovered that already at cellular levels, these internal clocks orchestrate the timing of proper hormone secretion, thus optimizing body metabolism by anticipating the rest-activity and feeding-fasting cycles. Their misalignment would thus favor the occurrence of metabolic diseases. Their discovery, to be read in the journal Genes and Development, highlights an essential factor, yet still poorly understood, which may explain diabetes development as a consequence of circadian misalignments of these cellular clocks.

Bad timing is depressing: Disrupting the brain's internal clock causes depressive-like behavior in mice -- ScienceDaily

Inherent circadian clocks help us function throughout the day, by telling us when to sleep, wake and eat, as well as by synchronizing our bodily processes. "It is perhaps not surprising that disruptions of our natural synchronization can have heavy impacts on our physical and mental health," Dr. Landgraf added. However, until now researchers did not know if disturbed circadian rhythms were a cause or consequence of mood disorders. In the new study, a team led by David K. Welsh has shown for the first time a causal relationship between functioning circadian clocks and mood regulation.

Midnight munchies mangle memory: Eating at the wrong time impairs learning, memory -- ScienceDaily

Some genes involved in both the circadian clock and in learning and memory are regulated by a protein called CREB (cAMP response element-binding protein). When CREB is less active, it decreases memory, and may play a role in the onset of Alzheimer's disease. In the mice fed at the wrong time, the total activity of CREB throughout the hippocampus was significantly reduced, with the strongest effects in the day. However, the master pacemaker of the circadian system, the suprachiasmatic nucleus located in the hypothalamus, is unaffected. This leads to desynchrony between the clocks in the different brain regions (misalignment), which the authors suggest underlies the memory impairment. "Modern schedules can lead us to eat around the clock so it is important to understand how the timing of food can impact cogitation" says Professor Christopher Colwell from the Department of Psychiatry and Biobehavioral Sciences at UCLA. "For the first time, we have shown that simply adjusting the time when food is made available alters the molecular clock in the hippocampus and can alter the cognitive performance of mice." Eating at the wrong time also disrupted sleep patterns. The inappropriate feeding schedule resulted in the loss of the normal day/night difference in the amount of sleep although the total time spent asleep over 24 hours was not changed. Sleep became fragmented, with the mice catching up on sleep by grabbing more short naps throughout the day and night.