ClockNews #32 - Infants, Adolescents, Doctors, Patients and Travellers

Cycled Light Promotes Growth in Pre-term Infants

A Duke University Medical Center study has shown that exposing babies born before 31 weeks of gestation to cycled light helps them grow faster, and the study identifies no short-term advantages to keeping infants in total near darkness, the standard practice with many infants.

Separating morning and evening in the circadian clock of mammals

A key question for circadian biologists concerns the way in which seasonal changes in day-length alter the behavior of circadian clocks over the course of the year. One idea for which evidence has accumulated is that circadian clocks contain coupled “morning” and “evening” oscillators that are separately synchronized to dawn and dusk.

Researchers discover stem cell 'guide' that may be key for targeting neural stem cell treatments

The protein, a small peptide called prokineticin 2 (PK2), was found to play a key regulatory role for the proper functional integration of these new neurons in the brain. A few years ago, PK2 was shown by the same research group to be an important regulator of circadian rhythms.

His numbers are in the ballpark

For years he's suffered from a sleep disorder that can turn his schedule upside down -- day becomes night, night becomes day. On several occasions, he had to cancel interviews because it was bedtime at 3 p.m. Van's response to his illness has been predictable: He's researched it intensively, and over time developed theories about the brain that he believes could earn him a Nobel Prize someday.

Early Function Of Specialized Neurons Marks 'First Light' In Retinal Maturation

The researchers found that, quite remarkably, the melanopsin-expressing ganglion cells are present in abundance and act as functional photoreceptors from the day of birth, when it has been widely assumed the mouse retina lacks photodetection. At the time of birth, a significant percentage of cells in the retinal ganglion-cell layer express melanopsin and respond to light.

Researchers Say Sleep Gene Related to Addiction

Not only does drug use disrupt sleep, but researchers say that a gene involved in regulate circadian rhythms could influence the addictive response to drugs like cocaine.

Shooting Down the Breakfast Club

There is an alternate—and perhaps more compelling—explanation for why breakfast-eaters do relatively well in school while breakfast-skippers may have a tough time: The skippers are also the ones whose bodies rebel against early-morning activity. Their circadian clocks are telling them that it's still nighttime, or they're plain exhausted and need the extra zzz's. Taken together, the scientific literature on breakfast and sleep suggests that making sure kids get enough shut-eye will probably do more for them than dragging them out of bed to eat their Wheaties.

Teenagers need help to form better sleep habits

Left to their own devices, teenagers sleep about nine hours a night, studies show. Generally, they go to bed later and wake up later than younger children and adults, perhaps due to hormonal-induced changes in circadian rhythm.

Exposure to daylight reduces hospital recuperation times

Building developers, architects, hospital and city planners, and interior designers take note: according to Dr. Asher Derman, building and design environmental consultant (Battery Park City, AOL-Time Warner), a small but important group of recent medical and health care related studies are beginning to link exposure to daylight and window views within buildings with decreases in recuperation times for hospitalized patients.

New Study Showed Ramelteon Helped Adults With Chronic Insomnia Fall Asleep, Sleep Longer

Ramelteon, a novel investigational compound under review with the FDA for the treatment of insomnia, reduced the time it took to fall asleep and increased total sleep time in adults with chronic insomnia, according to results from a Phase 3 study presented this week at the 19th Annual Meeting of the Associated Professional Sleep Societies (APSS). Results of the study also showed no evidence of rebound insomnia, next-day impairments or withdrawal effects due to discontinuation.

Sudden climate change is not just about Eskimos in bikinis

Take that marmot. The yellow-bellied marmot's hibernation habits are guided by ancient circadian rhythms that are cued by seasonal changes in light and temperature. Like their cousin Punxsutawney Phil, marmots awake from winter hibernation in underground burrows and surface when they sense the earth is warming. In recent years, conservationists report, marmots are emerging from their holes a month sooner than expected. But if the ground warms before deep snowpack melts, which is now often the case, emerging marmots cannot get to food and they starve.

Night and rotating shift workers sleepy

European workers who regularly work at night, and those who work rotating day and night shifts, are at high risk for excessive daytime sleepiness.

Fear and freedom when darkness fell -
Before electricity, night determined how we lived, loved and slept

Who knew that nighttime had a history? A. Roger Ekirch knows because for 20 years he has been working by artificial light in archives and libraries all over Europe to develop a picture of what it was like to live before gas, and then electricity, changed the nightscape into a mere extension of the worlds of work and play. "At Day's Close" provides a panorama of the night from the 16th through the 18th centuries, from Scandinavia to the Mediterranean, with an occasional foray into the North American colonies. Ekirch shows that in the early modern period, the rhythms of life were not what they are today and that Europeans of that period lived in two worlds: one ruled by light and the rules of society, and the other governed by anxiety, fantasy and a dreamy kind of community.
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The final section of "At Night's Close" underscores how even the biological rhythms of sleep have changed since the advent of gas and electric lighting. People slept differently in the early modern period because their circadian patterns had not been altered by the persistence of light beyond sunset. Ekirch is fascinated by accounts of "a first sleep," after which people would lie awake for long stretches of time before returning to their slumbers. He speculates that this gave them more ready access to their dreams, and he goes on to make the surprising claim that such access means that early modern people had a greater capacity for psychological insight than we whose sleep cycle has been modified by artificial light. Although his explanation for our supposed diminished capacity for psychological revelation is at best unpersuasive, it does seem quite right to recognize how lighting may have altered the state of our biology as well as our society.

Beauty sleep helps to drive the mind

Research conducted at the Dial-a-Bed Sleep Laboratory at Wits University in Johannesburg shows why winter-time rising is so much harder than in summer.

People with Outgoing Personalities are More Likely to Underestimate How Sleepy They Really Are

How Sleepiness Relates to Personality and Work Schedules is Examined in Two Abstracts to be Presented at 19th Annual Meeting of the APSS

European Working Time Directive May Put Doctors' and Patients' Lives at Risk

Recent studies from the United States have proved the risks to patients and doctors of long working hours. Any shift system should have as few successive night shifts as possible, with a maximum of three consecutive nights. A single night shift, with a day off before and after, is reported to show the least distortion of circadian rhythms.

Pakrasi to head Energy Department grand challenge

Specifically, Pakrasi's project will focus on the amazing cyanobacterium Cyanothece, a one-celled marine organism, the only bacteria with a circadian rhythm, or biological clock. In particular, Cyanothece has the uncanny ability to fix oxygen through photosynthesis during the day while fixing nitrogen through the night.

Incredibly, even though the organism has a circadian rhythm, its cells grow and divide in 10-14 hours.

"This is a mystery in biology," Pakrasi said. "Why does an organism do this and yet have a circadian rhythm? It must be that it gains something. We intend to find out."

To unravel the mystery, Pakrasi and his collaborators will be growing Cyanothece cells in photobioreactors, testing cells every hour to try to understand its light cycle at different times of the day. With the combined diverse expertise of 14 different laboratories, the scientists and engineers will examine numerous biological aspects of the organism.

Balanced Life: Why the body clock goes haywire with jet lag

Researchers in a study published in Current Biology zero in on the SCN in rats. They found that the SCN actually comprises two sections, dorsal and ventral. Rats were exposed to gradually changing light and darkness over a period of seven days, until they were in constant darkness. They looked at changes in the brains and discovered that the two sections of the SCN actually adjusted to the shifts in light at radically different rates. The ventral part of the SCN—which is connected to the light-sensitive retina—adjusted very quickly to the change in light. The dorsal part took days to adjust. The signaling pattern between the two sections gets confused, which sends all sorts of mixed messages throughout the body.

Sleep Deprivation a Serious Problem

One of the causes of a bad nights sleep is the interruption of our body's natural rhythms caused by changing light levels in our sleeping environment. One of the worst offenders is the television. Many people lie in bed and watch TV until falling asleep leaving the TV to play all night.

Afternoon classes might help increase teens performance

Skimping on sleep resulted in poorer school performance. Students reported feeling better in afternoon classes, and all of them did better at school in the afternoon than in the morning.
The researchers tried exposing some of the students to bright light in the early morning. Those light treatments didn't change the students' sleep cycles or academic performance, compared with a placebo.

Lack of sleep can affect teen athletic performance

Studies about sleep and circadian rhythms may have applications that extend outside the scientific arena and into athletic performance in young people.
Considering the negative effect of insufficient sleep on performance, one Rhode Island-based sleep expert concluded that sports teams traveling west may have the upper hand when playing on their rivals' home turf early in the day.

The importance of light in healthcare environments

Architect Mies van der Rohe stated: “The history of architecture is the history of man’s struggle for light, the history of the window.” However, in the rush to create commercially-viable and technologically advanced healthcare institutions, the importance of appropriate lighting has been forgotten and the cost of employing people outnumbers the cost of operating a lighting system by approximately 150 to one.

At the same time, the effect of light on our physiological systems cannot be denied; the human circadian pacemaker is extremely sensitive to dim light, with a light intensity equivalent to indoor room light able to significantly shift the timing of the circadian system. While the long term effects of inappropriate light exposure are under investigation, misalignment between the internal circadian pacemaker and the external environment is thought to contribute to health problems such as cardiovascular disease, diabetes, sleep and gastro-intestinal disorders.

New research explains jet lag

Turns out that your brain's master circadian clock is actually twins. When you're time-shifted, as in a transoceanic flight, one twin zips ahead of the other, resulting in jet lag.
Now, a University of Virginia scientist working with Dutch colleagues has pinpointed the "mother" neurotransmitter that makes the twins resume walking together side by side, putting your body clock back on track.

Weekend lie-in is part of growing up

TEENAGERS have been given the best excuse for lying in bed for hours at the weekend - it is part of their in-born cycle, according to new research.
A US study published yesterday in the journal Paediatrics found that early school starts were forcing students to perform academically at a time of day when they were at their worst.

Don't blame Kevin: It's his hormones

Biological changes at puberty make it difficult for adolescents to get the nine to 10 hours of sleep their bodies require, making them moody, lethargic and less alert, according to research published yesterday.
Teenagers who refuse to emerge from beneath their duvets until after midday at weekends are neither lazy nor anti-social - they are repaying their accumulated "sleep debt".

The 28 Hour Day

Here is an idea that sounds great on paper, especially if you are a techno-geek and don't go out much. However, this schedule ignores biology and will KILL you.

Reverend William Paley's Circadian Clock

I got homework to do. PZ Myers alerted me to an incredible argument that the existence of circadian rhythms denies evolution!

bryanm, the proprietor of the aptly-named The Narrow blog, describes himself as "...nobody who wants to tell everybody that there is somebody who can save anybody." In other words he is a know-nothing who keeps bothering everybody trying to push his idea that there is this non-existent being who can save anyone from whatever one wants to be saved from except from the nagging by bryanm. The other day, he wrote this post densely packed with nonsense. No need to look around the blog - it contains mostly stuff debunked here and here.

This is what bryanm writes in one of the comments to his post linked above:

Finally, let's look at circadian rhythms and the age of the earth. Investigation of nearly all of the earth's living organisms including microorganisms, plants, animals and humans) reveal the existence of circadian rhythms or biological clocks Numerous scientific studies have clearly deomnstrated that these circadian rhythms are not only widely present in all life forms, but are resistant to any and all external changes in the environment. Studies have shown that these biological rhythms are also endogenous or built-in genetically. How did these 24 hour rhythms get there in the first place? Obviously, they had to have been programmed initially into all biological life forms by the Creator (Jesus Christ) himself.

Arrrrggh! Where do I start? Let me dissect it first point by point, and finish with a Big Piture in the end.

Finally, let's look at circadian rhythms and the age of the earth.

Thankfully, PZ already debunked the "leap second" argument, so I don't have to deal with it here, but read the counter-argument here for your own edification. Although the length of the day did change somewhat over billions of years, the change is so slow, the day was NEVER shorter than about 18 hours. The rate of change is so slow that it is easy to evolve the changes if you needed to. But, you don't need to! Guess what? Even a well-buffered circadian system in a complex organism CAN entrain to 18 hour cycles! I did it in Japanese quail (Zivkovic et al. 1999). The confusion is between freerunning period and ability to entrain to environmental cycles. The day is 24 hours long. Endogenous circadian rhythms range between 16 and 32 hours in period, yet each one easily entrains to the 24-hour light-dark cycle. The endogenous period does not need to be equal to the length of the environmental cycle. Actually, a circadian clock with exactly 24 hours period will be VERY difficult, if not impossible to entrain. The mechanism of entrainment relies on daily correction of error - the difference between the endogenous and exogenous cycle is reset every day. For more, read the Entrainment posts here.

Investigation of nearly all of the earth's living organisms including microorganisms, plants, animals and humans reveal the existence of circadian rhythms or biological clocks.

First, circadian rhythms are ubiquitous in only four out of six big Kingdoms of Life (Animals, Plants, Fungi, Protists) and only a small group (cyanobacteria) from a fifth Kingdom (Bacteria) has evolved a circadian clock:

Archaea and most Eubacteria are arrhythmic. For Archaea, the explanation might lie in their ecology - they usually inhabit the most inhospitable regions of the planet including deep-oceanic hydrothermal vents, deep soil, rocks, salt deposits, polar regions, underground hot-water springs, where the rhythms of the planetary surface might not have any direct effect on their survival. Some Cyanobacteria have circadian rhythms as they need to temporaly separate incompatible reactions of photosynthesis and nitrogen fixation (Johnson and Golden 1999). Real Bacteria, being Prokaryotes, might just be capable of a rapid response to the direct environmental fluxes, and a timer might impose too rigid a control in, on their scale, essentially unpredictable environments.

In other words, circadian rhythms are adaptations of complex organisms to life on the surface. If you are too simple, or if you do not live on the surface, you do not need the clock. Circadian rhythms gradually decay in subterranean and cave animals (just like cave fish loose eyes).

The genes involved in circadian rhythms in the five Kingdoms are completely different, suggesting that the biological clock evolved independently five times in the history of life on Earth. The internal logic of the clock, though, is somewhat similar, usually involving some version of a transcription-translation feedback loop between clock genes that generates rhythms in the cell (and organism) which, in turn, feeds back onto the genetic feedback loop.

Looking at a complex circadian system, e.g., that of mammal, reveals not just great complexity, but also great redundancy: multiple copies of the same clock genes, one copy of which can always be "knocked-out" with no apparent effect on the workings of the clock. If you knock out all redundant copies out of a mammalian clock you will still have a functional, albeit much simpler, circadian clock that is VERY similar to that of a fruitfly.

It is much more revealing to look at the simplest clock, that of cyanobacteria. Cyanobacteria have a unique problem to solve: their life depends on succesful activity of two different biochemical processes - photosynthesis and nitrogen fixation. Unfortunately for them, these two processes are incompatible with each other, thus need to be separated. Most cyanobacteria have solved the problem by forming chains of bacterial cells. A division of labor evolves, in which each cell is able to remain relatively simple and specialized for one of the two processes. Some cells do only photosynthesis, others only nitrogen fixation. The two types of cells then exchange the final products (energy and nutrients).

However, a small number of cyanobacterial species (e.g., Synechococcus and Nostoc) have hit on a different solution. They do not form chains. Each cell performs both functions (and is thus more complex). Instead of spatial separation, they evolved temporal separation of the two processes: photosynthesis happens during the day (when sunlight is abundant) and nitrogen fixation is relegated to the night period. From what I remember from bacterial literature, about 2/3 of the genome is expressed ONLY during the day and about 1/3 of the genome is expressed ONLY during the night. This clock is, thus, just a simple ON/OFF switch: switches light-compatible genes on and nitrogen-fixation genes off in the morning, and the reverse in the evening. That does not sound irreducibly complex any more, does it?

Numerous scientific studies have clearly deomnstrated that these circadian rhythms are not only widely present in all life forms, but are resistant to any and all external changes in the environment.

The blades of knives, spears and swords had to be made very sharp, because our skins are resistant to hits by blunt objects. My body temperature is alaway around 37 degrees Celsius, no matter what the temperature is outside. My blood levels of Calcium are practically constant and taking TUMS does not change that. My blood pH is fantastically resistant to change, although I drink liters of highly-acidic Coke every day. Some people's brains are highly resistant to change by presentation of facts that challenge one's prior beliefs. Yet, all those systems have evolved. How does resistance to changes in the environment have anything to do with their evolvability? If brianm took a pill of Lithium, his endogenous freerunning circadian rhythm would dramatically change. Yet, that is not important - what is important is that brainm's circaidan rhythm, with or without Lithium, is highly malleable to environmental change: its "natural" period of about 25 hours is "forced" by a light-dark cycle to assume a 24-hour period EVERY DAY. Entrainment is the most obvious example of malleability of the circadian rhythms.

Also, brianm is confusing resistance at the time scale of an organism's lifespan and resistance at the time scale of evolutionary change. Even if endogenous rhythms were highly rigid within an individual, that has nothing to say about the ability of natural selection to alter its properties over many generations over a large period of time.

But they are not rigid even at the time scale of individuals. Most of my PhD dissertation (nothing published so no details here yet, sorry) is based on the study of individuals who exhibit marked day-to-day variability in period. Those individuals have been discarded by past researchers. I can now walk into the room with hundreds of quail and pick, with over 80% success rate, just by looking at them, which ones have stable rhythms and which ones have variable rhythms. I have even higher success rate in predicting who is who BEFORE they hatch out of their eggs! I can breed them for or against this trait - what more can one ask?

Studies have shown that these biological rhythms are also endogenous or built-in genetically.

which eliminates external factors, be it "Factor X" or Aliens or Designer-God. We know the genes and we have tracked how they evolved. Something being "genetic" makes it easier to explain by population genetics than traits not directly attributable to individual genes (e.g., emergent properties of a complex system).

How did these 24 hour rhythms get there in the first place?

I have written about it before:

There are three main lines of thought concerning the origin, evolution and adaptive function of biological clocks (Winfree 1990). The first view assumes that in the beginning the organisms were arrhythmic. The cyclic nature of energetic availability and cycles of potentially degrading effects of the sun's ultraviolet rays on particular pigmented enzymes, provided the selective environment. A cell with a timer can predict the changes and adjust its metabolic activities to minimize energetic and material loss. This cell will outcompete the other cells in the Archeozoic sea (Pittendrigh 1967). The emergence of such a system so early in the evolution of life leads to prediction that the molecular mechanisms of circadian rhythmicity will be highly conserved among all organisms (Winfree 1990, p.389).
The second view assumes that the environment itself forces rhythmicity onto the early unicellular organisms (Goodwin 1966). To economize waste, the cell evolves modifier genes. Each of these gene products will have a role in facilitating a smooth transition from one to the next phase of the imposed cycle. As more and more such genes evolve, every state of the cycle comes under genetic control. Three billion years later "the cell might surprise itself to discover...when some scientist first puts it into constant conditions, that it shuffles its way spontaneously through almost the same cycle" (Winfree 1990, p.390). So, even though all the cogs and wheels were, the whole clock itself was never selected for.
The third view states that all biochemical processes are cyclic. Furthermore, this cyclicity is part of the definition of life. Some of the cycles are regular, and the periodicity of such oscillations can be modified by natural selection (Winfree 1990, pp.391-392). Flexibility in counteracting stabilizing homeostatic mechanisms can add another degree of freedom in which to search for optimization. The second and third views expect to see almost as many circadian mechanisms as there are species. If one speculates that the life originated in the shallow tidal pools, than the circatidal rhythms might have been the first to arise, either before or simultaneously with the circadian clocks.
There is nothing incompatible between the three views. They could have conceivably all contributed to the emergence of timing mechanisms.

The problem in chronobiology is that the adaptive function of clocks is so obvious that it is difficult to get funds for rigorous testing of evolutionary hypotheses. The circadian clock is one of the best understood biological mechanims at the molecular level, so evolutionary relationships between the clock genes are too easy to see. Actually, I have lamented before that not enough rigorous evolutionary research is performed. For instance, I wrote this in 2001 as an answer to one of the questions on my written prelims, and posted it here as a blog-post later. Carl Johnson recently published a review with the same sentiment, ably reviewed by Heinrich, not Hindrocket on his blog, again voicing the same sentiment. The problem is not that it is difficult to explain the origin, evolution and adaptive function of clocks. It is the opposite - the embarassment of riches! So much is known. There is so much variation. There is such a good match between one's circadian function and one's ecology. It is the one biological property that I would pick to conveniently forget to mention if I was a Creationist.

Obviously, they had to have been programmed initially into all biological life forms by the Creator (Jesus Christ) himself.

How did Jesus Christ manage to create a world which he was to be born into a couple of thousand years later? I can see the argument that his Daddy did it, but Jeebus himself? Makes no sense. I like the use of the word "programmed" - I can just imagine the Big Hacker In The Sky playing with code on his huge computer that never freezes and gets no viruses ever. Is all of Creation just God's blog?

What brianm got hooked on was the term "biological clock". This is the favourite Creationist example ever since Paley wrote about the Watchmaker. What a coincidence: if there is no watch without a watchmaker, there cannot be a circadian clock without a circadian clockmaker. Hey! Just because we use metaphors and call a cell-component a machine that does not mean it actually IS a machine. It's a metaphor!

And, actually, it is a pretty bad metaphor. The circadian clock does not really work like a clock (and some people in the field have always grumbled against the use of the term). Its logic is more similar to a Rube-Goldberg machine. A few years ago my wife bought me a book containing all of the original examples of the Rube-Goldberg machines, but if you have not seen those, I guess you have watched a few episodes of a cartoon like Tom and Jerry in which Tom designs a machine in which one action results in the next and next and next until the last action traps Jerry. Here is an example by Rube Goldberg himself: Golfer pulls trigger shooting tee into ground at far end of a gun. Report of the gun causes a groundhog to run into a hole. Leash on the groundhog's collar pulls on the edge of a platform containing a cannon ball. Cannon ball drops on bulb causing atomizer to spray a shirt. Shirt shrinks, gently opening the attached ice-tongs that are holding a golf ball. Golf ball drops on the tee.

A mammalian circadian clock is like a hugely complicated Rube-Goldberg machine. But you can take away, with very little re-arrangement, piece by piece, all elements of the machine, until you are left with just a single simple switch that turns something on or off - like Tom simply jumping on Jerry, or a golfer simply placing a ball on the tee with his hand, or like a clock in cyanobacteria. This is a very very reducible complexity.