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(Wealthier) readers in biomedical science. Here’s your chance to contribute to something BIG: Epigenetics and sleep. How sleep amounts alter gene function as to be studied by an elite group of folks in sleep research

https://experiment.com/projects/can-sleep-patterns-change-gene-function

Welcome to SfN y’all!

First day and great day. Please venture over to the Theme H posters on display til Sunday. In today’s funding climate, it’s great to see an emphasis on teaching and the history of our field. There are different teaching modalities for different demographics and that is the key to success.

As for science, the clocks symposium was intriguing because people are finally getting optogenetics in the biological clock to work! And they work not just on one gene or protein but the entire system affecting neuron output and behavior. Golly, it was impressive!

Follow my other random thoughts and pics from the conf @beastlyvaulter on twitter and IG

Neury Thursday: Sleep and the Blood Brain Barrier, with some hesitation

The blood brain barrier (aka, BBB) can be a royal pain in the arse for pharmacologists and pharmaceutical companies. The ultimate goal of the neuro division of big pharm is to design drugs that can be taken orally and yet still cross the BBB with little issues. Billions of dollars can be gained or lost at the helm of the BBB. Well, new research in the recent issue of Journal of Neuroscience just introduced another conundrum for BBB permeability: sleep deprivation.

ResearchBlogging.orgThis BBB group in Louisiana investigated BBB permeability in lieu of chronic sleep deprivation on many levels. First, they found a reduction in glucose uptake by the brain, especially in regions that are in constant need of glucose like the cortex. Glucose uptake was measured by injecting radioactive glucose into the gut region and then measuring its transport up to the brain. A reduction in glucose uptake was complemented with a reduction in GLUT transporters which initiate the process of glucose being taken up by a tissue.

 

 

Glucose uptake compromised by sleep deprivation

The researchers also found an increase in COX-2, an enzyme involved in the initiation of pro-inflammation, with chronic sleep deprivation. This increase in pro-inflammation was accompanied by a decrease in forms of nitric oxide synthase which is responsible for vasodilation.

sleep deprivation interferes with vasodilation

 

What is most interesting is that all these pathologies disappeared with letting the mice get a day’s worth of recovery sleep. I’m a little skeptical about a day being enough to reverse a week’s worth of sleep loss even though the data reveals as such. But this is just the problem; we have no idea what the sleep deprivation protocol actually is and it is too difficult to interpret from the first figure! I’m starting to doubt that any of the reviewers are actually sleep researchers. It’d be acceptable for a middle-tier journal, but certainly not for a high-impact journal. One of the unwritten responsibilities of any reviewer is to ensure that the manuscript reads in such a way wherein the experiments can be replicated and the current hypothesis can either continue to be accepted or brought into question. The reviewers failed to do their jobs and the authors failed as scientists and now us readers of the flagship journal of the largest society of neuroscientists must scratch our heads and wonder what is so “unique” and ground-breaking about this protocol of chronic sleep deprivation that allows an animal and its body to recover in a single day.

He, J., Hsuchou, H., He, Y., Kastin, A., Wang, Y., & Pan, W. (2014). Sleep Restriction Impairs Blood-Brain Barrier Function Journal of Neuroscience, 34 (44), 14697-14706 DOI: 10.1523/JNEUROSCI.2111-14.2014
 

It’s still 1927, sometimes: Women in Science

What is unique about the picture taken in 1927 at the Solvay Conference: a gathering of the elite physicists and chemists of the time?

This is the gender diversity of most faculty departments, even ones close to home

 

Close up

There’s one lone female. In 1927, that was impressive, but if you look a many group photos from university departments in science, math, and engineering today, there is likely to be just one female for the same number of people as the 1927 Solvay Conference. Now that is pathetic.

Eleanor Roosevelt and Marilyn Monroe often said that “well behaved women rarely make history.” It’s true, even in an academic setting. Fortunately, academic departments make it easy for women to be viewed as misbehaved or notable. Often times, if I consider alternative interpretations and approaches from senior scientists, I’m viewed as “lacking in confidence ,” but if I become overly passionate about an issue and don’t change my opinion after hearing alternative viewpoints, “I’m being defensive.”

Some of the more ludicrous commentary that I have heard about from female colleagues is being begged by administration to not have children so as not to increase risks for postpartum depression.

And then of course there is sexual misconduct. One world-renowned neuroscientist made himself “Instagram/Twitter/Facebook famous” at the Society for Neuroscience annual meeting in NOLA in 2012 by lamenting about the lack of attractive females at the meeting. It may had been the booze and easy access to prostitution talking or the fact that we shared the convention center with a boating trade show, but still. A recent report in PLoS found that at least 50% of women encounter some form of sexual harassment, verbal or physical, at some point in their professional career.

Now how can we overcome?  My colleague and mentor of mine, Dr. Jenny Marcinkiewicz, who has served on STEM- and women in science-related tasks forces recommends the following, “We can educate both our male and female colleagues about the dangers and inequity of unconscious bias. We can continue to fund ADVANCE grants from NSF that work to advance the careers of women in science. We can push to create women’s taskforce groups that identify actions to be taken and then make sure these are implemented. IMHO, asking women to work harder and stop making excuses is part of the problem, not part of the solution. It serves to drive capable women out of the sciences. Last, but not least, postpartum depression is not a choice and cannot be solved by simply willing ourselves out of it or working ourselves out of it.”

Vampire Diaries: Tales of Sleep

Blood is making a comeback in neuroscience and psychology research. Centuries ago, Galen thought that personality and behavior were governed by the four “humors” with blood being one of them. A few months ago, blood gained some credibility in neuroscience when a study published in Nature found that the donation of blood collected from a young mouse to an old mouse forestalled neurodegeneration while donation of blood collected from an old mouse to a young mouse accelerated neurodegenetaion. Read the full details in this blog post.

ResearchBlogging.orgAs for how the blood may carry sleep-promoting factors that cross the brain and act on sleep regulatory areas, there may be a few. Recently, researchers at UPENN have undertaken an extensive study where they collected the blood from individuals sensitive or resistant to sleep deprivation. The researchers deprived the subjects of sleep for 38 hours and figured out just how sensitive or resistant the subjects were to sleep deprivation through a simple, reliable test of mental alertness and lapses: the psychomotor vigilance test. Performance on the PVT was compared against the blood genome of these individuals. The results were striking in that it pointed out that most of the genes were more sensitive to time-of-day, a circadian effect, rather than the environment challenge of sleep deprivation, a homeostatic effect. Separating circadian and homeostatic influences on daily sleep amounts is a constant struggle. In this study, the researchers were able to identify circadian vs. homeostatic influences without even controlling for these processes through a unique protocol called forced desynchrony. There were two genes that showed sensitivity to sleep loss in that their gene expression increased across a protocol of sleep deprivation, but for the most part, the genes peaked in the mid-night or mid-day which conveniently correspond with biologically driven dips in core body temperature. However, the rhythms of this waxing and waning of gene expression was dampened in the lucky bastards who are resistant to changes in mental performance with sleep deprivation.

And so while this study has narrowed down some possibilities, the quest for a single, peripheral regulator of sleep centers in the brain continues. Hopefully I am the first to find it.

Vampire Diaries is a bore

Arnardottir, E., Nikonova, E., Shockley, K., Podtelezhnikov, A., Anafi, R., Tanis, K., Maislin, G., Stone, D., Renger, J., Winrow, C., & Pack, A. (2014). Blood-Gene Expression Reveals Reduced Circadian Rhythmicity in Individuals Resistant to Sleep Deprivation SLEEP DOI: 10.5665/sleep.4064

Sleep Position Matters.

Today, I got a deep tissue massage in an attempt to accelerate recovery from the Pensacola Beach Brawl. It is no surprise that I favor my right side; it is my dominant side. Even so, my massage therapist provided some insight that is so obvious yet so neglected and likely explains my long-term aches and pain on my right side; I may be sleeping wrong. Duh! If you are like me who needs lots of restorative, deep sleep in an attempt to recovery for a hard day of training, then your body doesn’t really care what position it sleeps in because it is too busy getting this restorative, deep sleep. Therefore, we have to prepare our bodies to sleep in a healthy position before we sleep and are immobile for nearly 8 hours. Fortunately, Kelly Starrett, pioneer of mobility WOD, has addressed this:

Pensacola Beach Brawl: Pain in the Sun, Sand, and Surf

It’s time for some self promotion mixed with science. Sorry. This weekend, I competed in the Pensacola Beach Brawl which also presented me with the opportunity to compete in my first (Crossfit-style) triathlon. Sure, we swam (and saw a bull shark on the pier the morning of the swim), but then we sat on a stationary bike to be one with our thoughts, a remarkable view of the Gulf coast, and the dinging of the bike in an attempt to forget how few calories we had biked and how much further we had to go: 150 calories in total. From there, we hopped over a small wall and began the worst part of the tri; a seemingly endless run for a mile in the soft sand that is difficult to walk in let alone run in. It really jacked up our heart rates.

And we are off

Kill Em

The final push

I finished 5th overall which I was extremely happy with because it was my first legitimate ocean swim.

After a night of recovery, it was on to a standard Crossfit competition on Saturday. Unlike most Crossfit competitions in Georgia, this was outdoors. The rain even held off for us. Not only did I tie my current PRs for my Olympic lifts (clean and snatch), but I did really well in the metabolic conditioning workouts that tested our latencies to forearms and bicep fatigue as well as how much pain we could handle after a long, enduring weekend. We also had to NFL combine style testers; max bench press reps at bodyweight and the standing broad jump. I would have been embarrassed if I didn’t place top three in the broad jump. Luckily, I did place first, helping secure a 6th place overall finish for the weekend.

New hang snatch PR

Tie of clean PR

Thrusters to start

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Deep concentration

The last workout

On Sunday, I was part of a local Georgia team from Crossfit Perimeter. The workouts were seriously modified due to the poor weather but honestly, I was thankful. We took full advantage of the beach by doing a mile run as a team as well as dragging an #80 sled 125 m each. It was nasty. Like most heavy, longer sled pulls, it is best to go slow and steady instead of going “all out.” Once your body switches over to fat metabolism, there is a serious compromise in power. This decline in power usually results from giving 100% effort in the beginning because you burn through your creatine and glucose reserves quickly.

Quad Squad

Overall, I had a fantastically grueling yet entertaining weekend competing, laughing, and hanging out with fellow Southeast athletes. Much thanks to the continued support of Boxstalker and Pure Strength –as we continue our journey to the podium in the 2015 Reebok Crossfit Games. The Pure Strength rig at the competition was awesome. And now it is back to lab bench.

The elite ladies

Panda Rage

In case you didn't know

History of Sleep by the Father of Sleep, Himself

Last week, my undergraduate advisor, Dr. Mary Carskadon, who could arguably be called the “mother of sleep” given her long-standing contributions as a female scientist, sent me the following article.

The article is about the life’s work of William C. Dement who many regard as the “father of sleep medicine.” I won’t spoil the contents of the article, but Dr. Dement should be any scientists’ idol, not just for those who study sleep. He has done basic science, translational science, clinical science, and is one of the most effective advocates for funding. Believe me, his numerous stories about trips to Capitol Hill are very humorous and could make for their own memoir. I first met Dr. Dement during the summer of my junior year (of college) as a Dement Fellow in Dr. Carskadon’s laboratory at Brown University. The advice he parted about the history of our field, doing science, and being a scientist have stuck with me today. I have passed along many of his stories and experiences to my own students at Morehouse College. So please, read Dr. Dement’s story. It will inspire you, scientist or non-scientist.

Dr. Dement with the 2006 Dement Fellows

For Sleep but Sleepless in Lake Arrowhead, California

For the past week, I have been residing in high altitude at the UCLA-owned resort of Lake Arrowhead, California in the San Bernardino Forest (and mountains) near LA. I was attending a scientific and professional development workshop devoted to sleep research, grantsmanship, responsible conduct of research, and networking. The theme of the workshop was “translational validity in sleep research” meaning that the focus was on appropriate animal models of sleep and disease states. The workshop has been going on for nearly 30 years organized, funded, and hosted through the efforts of Dr. Michael Chase of UCLA. Holy cow was it spectacular. I can see why my undergraduate advisor, Dr. Mary Carskadon, uses Michael’s retreat as a model for her annual retreat.

The trip began with a short trip to Manhattan Beach, its epic dining, and the Santa Monica Pier where I showed those beach boys that they really aren’t as strong as their muscles make them out to be.

When we arrived in Lake Arrowhead, we immediately began to dive into intellectual discussion. We went over and critiqued common methods to sleep deprive animals. We weighed the pros and cons of common animal models of sleep and disease, namely the fly, rat, mouse, and even cat. We even talked about the pros and cons of staying ahead of the curve. The general consensus is that it is never good to put the cart before the horse; that optogenetics and chemogenetics, two sexy approaches in neuroscience that I have discussed previously, are worthless in time and money if you do not have a sufficient hypothesis and supporting rationale. Also, using these tools is not a priori for getting funded. We also learned about some transfection techniques for activating neurons and measuring neuron activity by transfecting a rabies virus or using a recording electrode covered in a lipophilic (fat-loving) material, enabling it to be sucked up by the neuron’s membrane.

On the morning of the second day, I organized a morning boot camp. One of the workshop’s organizers, Dr. Mark Opp, had the brilliant idea to do our workouts on the zen deck. Not a bad view, eh? The zen deck was the meeting spot for our morning boot camp/bro sessions for the rest of the meeting. On the second day, I also got too cocky (and stupid) in the pool and smashed my nose on the bottom of the deep end after doing a perfect front tuck into a dive.

The Zen Deck

The scientific sessions of the workshop continued with discussions of appropriate measures of sleep homeostasis. The obvious candidates are NREM sleep saturated with slow wave activity, but Dr. Ron Szymusiak presented evidence for physiological phenomena relevant to sleep homeostasis that have been overlooked. Basically, his lab examined the firing rates of neurons in two sleep-promoting nuclei of the hypothalamus, the ventrolateral and median preoptic nuclei. Typically, these nuclei are less active during wake and even forced wakefulness, and more active during spontaneous sleep or recovery sleep after sleep deprivation. Thankfully, Ron found that this is not entirely true because a tipping point from low to high rates of firing in these nuclei can occur across an episode of forced wakefulness. I am thankful for this data set because it addresses a concern that I have had with a data set of mine that I am hoping to be publish soon.

We also had an evening discussion on ethics. Each discussion began with a short skit. Here is the skit that my group and I performed to exaggerate very inappropriate relationships between mentor and mentee.

About halfway through the conference, we were introduced to the EUREKA grant writing proposals. Basically, we were given 36 hours to write AND present an R21 (NIH system) grant that would allow for two years of work and $250,000 in allowance (excluding whatever indirect costs the university took which is normally around 50%). The committee did a fantastic job of spreading out areas of research focus, or maybe it was just a coincidence. Our group had an interesting mix of expertise and personality. However, we were able to overcome an initial mental block in proposing a hypothesis-driven research question. Our proposal aimed to investigate how sleep deprivation could further worsen brain connections and cognitive and motor learning after a stroke. At the end of the day, our grant proposal won, although all of the proposals were impressive for the short time allotted! For our winning efforts, we got a bottle of Glenvelvet.

Presenting our grant

Winners of the EUREKA grant with their prize!

Without a doubt, this workshop was one of the best smaller conferences in animal research that I have ever attended. It presented many opportunities to ask questions, respectfully refute opinions, and to remove the typically intimidating barrier between PIs and trainees.  The countdown til the next workshop is on.

A non-invasive system to replace EEG/EMG recording of sleep

This week, we resumed our biweekly journal club in sleep and circadian rhythms for the year. I presented a paper published last week in the journal Sleep. It was more of a methods papers, but still important because non-invasive tools for measuring sleep have become best-sellers: FitBit, Zeo, and other Nike/iPod-based physical activity software. This new technology that I talked about in journal club is reserved only for rodents although the researchers state that it could eventually transform the human sleep laboratory. The system, known as the piezoelectric system, has been around for about a decade, but has really only been used by selective groups. However, now that the system is commercially available (Signal Solutions), there may be more papers using it to record sleep. Hopefully, these researchers are cautiously doing so as I will explain why.

ResearchBlogging.orgThe hardware of the piezo system is fairly straightforward. There is a polymer “mattress” placed under a light layer of bedding on which the animals move around, groom, sleep, eat, drink, etc on. This polymer is connected to a box that encases the animals’ cages. The box also contains many tiers of infrared beams to measure general locomotion. Basically, the amount of mechanical pressure generated from movement and breathing is proportional to the amount of electric signal generated. These two variable–mechanical pressure and electrical signals–are assigned a score that is above or below a “wake” threshold shown here. The lower the positive score, the deeper the stage of sleep and the higher the negative score, the more intense the stage of wake.

Basically, these researchers found that the temporal distribution of sleep and wake across multiple days is largely in agreement between this system and the traditional EEG/EMG system that also requires someone to score each individual epoch of recording, a process that can take hours to days.

Decision Statistic determining sleep or wake

There were some concerns about over-reporting sleep during the light or rest phase of rodents as well as the system being a poor measure of particular EEG waveforms characteristic of each state of sleep and wake.

Temporal distribution of sleep and wake with EEG and this new non-invasive piezo system

But for the most part, I do think this is an ideal system for high-throughput research requiring quick sleep-wake analysis in hundreds of mice. It also removes human error of scoring sleep records out of the equation. Obviously, there are some limitations as to what types of studies should rely on the piezo system alone. Personally, I think it is ideal for high-throughput studies of drug screens. If you are interested in gross changes in sleep from baseline levels, then sure. But if you are trying to identify a new model of sleep dysfunction then this system may not be sufficient enough to accurately identify brief awakenings as sleep or wake. Regardless, I do hope to see more studies using this type of recording technology soon.

Mang GM, Nicod J, Emmenegger Y, Donohue KD, O’Hara BF, & Franken P (2014). Evaluation of a piezoelectric system as an alternative to electroencephalogram/ electromyogram recordings in mouse sleep studies. Sleep, 37 (8), 1383-92 PMID: 25083019

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