ClockNews #7: Restless Phantom Leg, Sleep Books and more on the randomness

Case of the week: Restless legs meet phantom limbs (hat tip to Majikthise)
http://majikthise.typepad.com/majikthise_/2005/01/case_of_the_wee.html

INTRODUCTION: We present the case of a patient who, after
amputation of both legs, suffered restless legs syndrome (RLS). This syndrome is
characterised by a feeling of agitation in the legs and an overwhelming need to
move them.

Collection Development: A Good Night's Sleep
http://www.libraryjournal.com/article/CA491144

Humans spend about one third of their lives sleeping.
Indeed, we can live longer without food than we can without sleep. (Adults
require an average of six to nine hours a day.) Yet despite decades of research,
scientists still aren't entirely sure what goes on during sleep, how it evolved,
or why we need it. They do know that sleep deprivation and untreated sleep
disorders cause car crashes, industrial accidents, poor work performance, and a
host of other problems.
Unfortunately, the convenience of living in a 24/7
society where work, shopping, and entertainment can be accessed at any time has
exacerbated sleep problems in this country. Is it any wonder that excessive
daytime sleepiness and insomnia affect some 60 million Americans?

Listed are several good books about sleep and various sleep disorders, including insomnias, narcolepsy and restless leg syndrome.


Researchers simulate molecular biological clock, New York University
http://www.medicalnewstoday.com/medicalnews.php?newsid=18918

Researchers at New York University have developed a model of
the intra-cellular mammalian biological clock that reveals how rapid interaction
of molecules with DNA is necessary for producing reliable 24-hour rhythms. They
also found that without the inherent randomness of molecular interactions within
a cell, biological rhythms may dampen over time. These findings appeared in the
most recent issue of the Proceedings of the National Academy of Sciences (PNAS).
Daniel Forger, an NYU biologist and mathematician, and Charles Peskin, a
professor at NYU's Courant Institute of Mathematical Sciences and Center for
Neural Science, developed a mathematical model of the biological clock that
replicates the hundreds of clock-related molecular reactions that occur within
each mammalian cell. Biological circadian clocks time daily events with
remarkable accuracy--often within a minute each day. However, understanding how
circadian clocks function has proven challenging to researchers. This is partly
because the 24-hour rhythm is an emergent property of a complex network of many
molecular interactions within a cell. Another complication is that molecular
interactions are inherently random, which raises the question how a clock with
such imprecise components can keep time so precisely. One way to combat
molecular noise is to have large numbers of molecular interactions, but this is
limited by the small numbers of molecules of some molecular species within the
cell (for instance, there are only two copies of DNA). To simulate the random
nature of the biochemical interactions of the mammalian intra-cellular circadian
clock, Forger and Peskin used the existing Gillespie method. The method tracks
the changes in the integer numbers of each type of molecule of the system as
these biochemical reactions occur. Modeling each type of molecule separately
helped avoid mathematical assumptions in their model that may not be valid in
real-life cells. Their model was validated with a large library of data on the
concentrations of the molecular species within the mouse molecular clock at
different times of the day and data on the behavior of mice with circadian clock
mutations. The results of their computer simulations showed that reliable
24-hour timekeeping can only be achieved if the regulatory molecules that
influence gene expression bind and unbind to DNA quickly--typically, within a
minute. In this way, the large number of bindings and unbindings helps to
compensate for the small numbers of molecules involved. The researchers also
found that having more molecules in the cell does not necessarily lead to more
accurate timekeeping. Removing all the CRY1 molecules (CRY1 mutant) or removing all the CRY2 molecules (CRY2 mutant), while keeping all other molecular species
unchanged, leads to more accurate timekeeping. While simulating the PER2
mutation, they found that circadian oscillations could only be sustained in the
presence of molecular noise. This may help explain some of the conflicting
experimental reports about the PER2 mutant. "Without the rapidity of molecular
interactions within these cells, the precision of the biological clock would be
lost," explained Forger. "It is remarkable that a process occurring on the time
scale of minutes can have such a profound effect on one that occurs over 24
hours."