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The Emotional Gyri & Sulci

The surface of the cortex of the human brain (and many other mammals as well) appears as a series of folds. The hill-like peaks of the coretx that is visible is refered to as the gyri (gyrus for a singluar "hill"). Each valley (seen on the surface as a gulley) is called a sulcus (sulci when speaking in the plural). So, my title for this essay is my neuroscience spin on the old adage "The Emotional Hills and Valleys".

As I sit here in my back office, very early this morning, I have decided to place a mirror in front of me (actually just to the side of my monitor) so that I can gaze at my old, furry visage as I type and perhaps glean some new insight into who I am and what my purpose is in life. I have already gone walking, having decided to see if a night without sleep will reset my emotional clock (there is evidence that working through the night on an OCCASIONAL basis may reset circadian rhythms and perhaps mood). Now I am smoking my pipe, filled with a robust burley tinctured with just a hint of raspberry. As I slowly exhale a lungful of the smoke and watch as the curls of the smoke cascade through my mustache hairs, I see a tired, yet hopeful face. I have felt rather rough and out of sorts emotionally for the last two days, but am hoping that things will improve. The beard on my chin is so grey. Perhaps I should color it to see if that improves my outlook? Nah. I think the grey suits me.

Well, let us see what the day brings.

PipeTobacco

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The Key To Longevity

The following report was filed today by ScienceDaily and looks at longevity in yeast. Well, my major professor back in graduate school always proclaimed that the essential four food groups were sugar, alcohol, nicotine, and chocolate. Well, it looks like he may have been on to something afterall. Yeast, famous in making our beer, our wine, our bread does so though the well known process called "alcoholic fermentation" that most 6th graders have heard about in school. Unfortunately, it may very well be that in our modern society of too easy access, we may not be activating these pathways often enough. See for yourself:

Starve A Yeast, Sweeten Its Lifespan: Molecular Mechanisms Link Sugar Production And Longevity

ScienceDaily (Mar. 30, 2009) — Johns Hopkins researchers have discovered a new energy-making biochemical twist in determining the lifespan of yeast cells, one so valuable to longevity that it is likely to also functions in humans.

Their findings, published in the March 20 issue of Cell, reveal that making glucose is highly influenced by a large enzyme complex already known to fix damaged DNA, and which apparently affects yeast life span through a common chemical process—acetylation.

In a series of experiments, the Hopkins team showed that when continuously acetylated, the so-called NuA4 enzyme complex causes yeast cells to live longer than they would under normal conditions.

The team genetically modified yeast cells, designing one to mimic the constantly acetylated form of the enzyme and another to mimic the constantly de-acetylated form. Then they compared these two mutants to a cell in which nothing was genetically altered. They found that the constantly acetylated form of yeast cell can outlive the unaltered cell by 20 percent and that the constantly de-acetylated form had an 80 percent reduction in its lifespan compared to the unaltered cell.

"Because the NuA4 complex is highly conserved among species, what we've found in yeast translates to humans as well," explains Heng Zhu, Ph.D., an assistant professor of pharmacology and molecular sciences at the Johns Hopkins University School of Medicine. "What we've revealed about longevity in yeast perhaps someday can translate to human health," he added.

Using a yeast proteome chip — a glass slide containing 5,800 or more than 80 percent coverage of all of the yeast-encoded proteins — the researchers hunted along this string of proteins to find specific molecular targets of the NuA4 complex.

By analyzing the yeast proteome chip and noting which proteins had an acetyl group stuck to them after adding NuA4, the team identified more than 90 such possible targets. To figure out which of these would naturally be acetylated, the team chose a random set of 20 to test further, ultimately confirming 13 as targets of the NuA4 complex.

More than simply expanding the list of known targets from three to 13, the team provided the first evidence that acetylation controls the activity of an enzyme called Pck1p, critical to sugar production in yeast and probably human cells. This enzyme is also controlled by the enzyme Sir2, which removes the acetyl group. Sir2 is heavily implicated in aging and a number of diseases by recent studies in mammals.

"The new function we identified for Pcklp is regulation of glucose-making, which is what all cells do to survive under conditions of starvation," Zhu explains.

Funded by the National Institutes of Health Roadmap Program, this interdisciplinary study involving biochemistry, proteomics, genetics and computational biology is a product of the High Throughput Biology Center, or HiT Center, of Johns Hopkins' Institute for Basic Biomedical Sciences.

In addition to Heng Zhu, authors on the paper are Yu-yi Lin, Jin-ying Lu, Sheng-Ce Tao, Jun Wan, Jiang Qian and Jef D. Boeke, all of the Johns Hopkins University School of Medicine; Junmei Zhang and Yingming Zhao of UT Southwestern Medical Center; and Shelley L. Berger, Wendy Walter and Weiwei Dang of The Wistar Institute.

* * * * *

While I had hoped for added incentive to eat more yeast-laden foods (beer, wine, bread), the actual message is to try to activate these pathways in ourselves as a possible mechanism to increase longevity. I truly believe that one of the most important things we can strive for to improve our health is to try and work to have a normal BMI reading. I am of the opinion that stress & obesity are the two factors most in the US need to address to improve the quality of their life.

PipeTobacco

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Day 185

Today is day 185 of my walking. I am heading out the door right after I write this note. Walking with such consistency is a very valuable and helpful thing I do for my soul. This may be even more important for my soul than it is for my body.

PipeTobacco

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Rough Sunday

I wish I could understand emotions better. After a wonderful Thursday, Friday, and Saturday, Sunday turned into a horror. My wife was in a bad mood for reasons she does not wish to explain to me.

I went for my early morning walk and then drove my truck down to get bagels, cream cheese, hot cocoa, and some soft-serve ice cream for a special treat on Sunday evening. Upon my return, I noticed my wife was acting "in a mood". I asked her to come sit with me on the couch, and I asked her, "What was wrong?" She said "nothing" and didn't seem to want to discuss it. So, I worked on preparing breakfast, and then she and I sat down again and we discussed the plans for the rest of the day. Basically we said we would work together on making dinner for the evening, then we would work on cleaning the house, and then we would go to the banquet with my mother-in-law & father-in law for our bowling team as it was the last day of bowling.

Well, we ate and had a very good breakfast. I helped clean up, and then started working on the vegetable rice dish I was planning to accompany dinner. My wife went off elsewhere. I went to her and reminded her we were planning to work together to get food ready. It was then that she snapped at me in a way that I find VERY, VERY upsetting.

I have learned over the years that my natural inclination at this point is to sulk and become angry quietly in the corner. However, I did not do that. Also, I did not get angry and yell or holler (which I have tried in the past, which also does not work). What I did do, was tell my wife to come with me privately to our bathroom. I was hurt, angry, and on the verge of being livid. But I spoke to her and chose my words carefully and told her that I did not like her snapping at me. I did not feel it was justified or fair. And I told her it made me feel hurt and angry.

Sometimes, when I try to be as upfront and careful about my words this will work and things improve. Unfortunately, they did not. I am still in amongst the chaos at this time.

PipeTobacco

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Genetics of Obesity

Today in the ScienceDaily, excerpts of a new report on the genetic factors related to obesity are described. The actual research article is in the journal, Cell.

Mice With Disabled Gene That Helps Turn Carbs Into Fat Stay Lean Despite Feasting On High-carb Diet

ScienceDaily (Mar. 23, 2009) — Researchers at the University of California, Berkeley, have identified a gene that plays a critical regulatory role in the process of converting dietary carbohydrates to fat. In a new study, they disabled this gene in mice, which consequently had lower levels of body fat than their normal counterparts, despite being fed the equivalent of an all-you-can-eat pasta buffet.

The authors of the study, to be published in the March 20 issue of the journal Cell, say the gene, called DNA-PK, could potentially play a role in the prevention of obesity related to the over-consumption of high-carbohydrate foods, such as pasta, rice, soda and sugary snacks.

DNA-PK, which stands for DNA-dependent protein kinase, has already been the subject of much research because it helps repair breaks in the DNA. Suppression of DNA-PK has been used as a technique by researchers to enhance the ability of cancer treatments to kill tumor cells. Its role in fat synthesis, then, came as a surprise to the UC Berkeley researchers.

"It turns out that DNA-PK is critical to a metabolic process we have been trying to understand for 20 years," said Hei Sook Sul, a professor in UC Berkeley's Department of Nutritional Science & Toxicology and head of the research team behind these new findings. "For the first time, we have connected DNA-PK to the signaling pathway involved in the formation of fat from carbohydrates in the liver. Identifying this signaling pathway involving DNA-PK brings us one step forward in understanding obesity resulting from a diet high in carbohydrates, and could possibly serve as a potential pharmacological target for obesity prevention."

After a meal of pizza and soda, it is known that levels of blood glucose - the digested form of carbohydrates - go up. That rise in blood glucose triggers the secretion of the hormone insulin, which helps different cells in the body use glucose for energy. Glucose in the liver that isn't burned for energy turns into fatty acids, which then circulate to other parts of the body, primarily to fat tissue.

This conversion of excess glucose into fatty acids occurs in the liver, but the exact molecular pathway involved has not been fully understood until now. Researchers have known that insulin binds to receptors on the liver cells, which activates protein phosphatase-1 (PP1), the first molecule of the insulin-signaling pathway inside the liver cell. Sul's lab had previously shown that upstream stimulatory factor (USF) is needed to activate certain genes, such as fatty acid synthase (FAS), which converts glucose to fatty acids.

The link between PP1 and USF was still a mystery until Roger H. F. Wong, a UC Berkeley graduate student in comparative biochemistry in Sul's lab, finally connected the dots through proteomic sequencing. He found that DNA-PK, which is regulated by PP1, controls the activation of USF and the subsequent conversion of glucose to fatty acids.

"The missing link was DNA-PK," said Wong. "We determined that DNA-PK acts as a signaling molecule in the chain reaction that begins when insulin binds to receptors on liver cells. This helps explain why untreated Type 1 diabetics, who cannot produce insulin, may experience significant weight loss. Without treatment, they basically have trouble making enough fat."

"This insulin-signaling pathway is also disrupted in Type 2 diabetes, in which the body still produces insulin, but the cells become resistant to its effects," said Wong.

After identifying DNA-PK, the researchers put the gene to the test in mice fed a diet containing 70 percent carbohydrates, but no fat. A typical lab mouse diet is made up of both fat and carbohydrates. Half the mice had the DNA-PK gene disabled, and the other half comprised a control group of normal mice.

"The DNA-PK disabled mice were leaner and had 40 percent less body fat compared with a control group of normal mice because of their deficiency in turning carbs into fat," said Wong. "The knockout mice were resistant to high carbohydrate-induced obesity and had lower plasma lipids, which can reduce the risk of cardiovascular disease. With all of these health benefits, this gene can serve as a potential pharmacological target for obesity prevention."

The researchers noted that although interest in low-carb diets persists, there are many sources of carbohydrates, including fruits and vegetables, legumes and whole grain breads and pastas, that have important nutritional benefits.

"The best way to control your body weight is to eat a well-balanced diet and limit your caloric intake," said Wong. "We hope that this research will one day help people eat bread, pasta and rice and not worry about getting fat."

This study is part of the larger research effort by the Sul lab to understand the molecular mechanisms underlying the synthesis of fatty acids, creation of fat cells and how fat is stored in the body. Recently, the lab published a study in the journal Cell Metabolism describing how a molecule called Pref-1 blocks the creation of fat cells. Two months ago, the discovery by Sul's lab of an enzyme called AdPLA critical to the breakdown of fat cells, was published in the journal Nature Medicine. This latest paper in Cell details the very first step of fat synthesis - making fat from carbohydrate.

Other co-authors of this study are members of Sul's lab and include several undergraduate students in the Department of Nutritional Science & Toxicology.

The National Institutes of Health helped support this study in Cell.

It is indeed interesting to understand how our bodies have evolved to keep us alive, and how sometimes our bodies are TOO good for the current environment at helping us in this pursuit. It would be better in this time of abundant food to have a genetic makeup that is less efficient at converting and storing calories.

PipeTobacco

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Nice Day in the "Big City"

Yours truly is now a "roving reporter" of sorts as I am away from my home territory and posting to you from the scenic site of the science research meeting I am currently attending. Lest you imagine I am in a tropical oasis, I am not. This year's meeting is being held in a northern climate city much like the one I hail from. Yet, for us, it is a nice, rather balmy day of 50 degree Fahrenheit weather (this is 10 degrees Celsius for those of you less comfortable with Fahrenheit).

Thus far, the meeting is moving along well, although it is early. Last night's Executive Board meeting was adequate, and a few stiff drinks eased my mind into a comfortable state. I hope my students both do well in their presentations. I am keeping my fingers crossed.

PipeTobacco

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Busy Day of Work Travel

Today's post will be a bit brief as I am preparing to travel to a scientific meeting today and will be there through the weekend. I *do* anticipate updating this site on Friday and also perhaps on the weekend as well as there will be ample computer connections available.

I have two students who are going to present our research at this meeting and I am a member of this science society's Executive Board as well, so I should be busy. In some ways a trip of this nature is good in that it breaks me out of my routine, and forces me to socialize in ways I typically do not routinely gravitate towards. Yet the hard part of this type of trip is that I will be away from my beautiful family. I shall miss them greatly while I am away.

PipeTobacco

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Exercise Day 178

As of this moment, I cannot say for certainty what it will feel like to reach the 178 milestone. Unfortunately, as I write this, I have yet to actually exercise. But, I am going to find some way to accomplish the walk so that my "days of consistency" remain intact. That NUMBER is a huge motivating factor for me. I would have sloughed off or just given up on walking a number of times if it were not for that number.

Perhaps I should apply that "number" idea to all aspects of my life? Perhaps it would keep me focused and more successful. The number of consecutive days I am happy? The number of consecutive days I accomplish my day's list of work efforts? The number of consecutive days I am able to bed my wife (no, that would not be appropriate and my wife would skin me alive)?

PipeTobacco

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Edgy & Sad

As much as I would like to report otherwise, if I were to assess my emotional mood and demeanor at the moment, I would have to describe it as feeling "edgy, sad, and stressed". I am not sure why I am (and have so often of late) felt this way concerning work. I currently am in "hiding" in one of my back offices so that I can try to get some real work done. Yet, even here, with the quiet, I have difficulties. 1. A student who does work occasionally back here for me has interrupted me twice. Not in any sort of problematic way. In fact, the student is very nice. But the interruptions disrupt my train of thought in ways that increases my "edgy" feelings. 2. I am on a very antiquated computer (an older cast off that I was able to obtain) that is barely able to run Windows XP (our U has decided to stick with XP instead of the current Vista due to computability issues across campus and will likely work to adopt whatever develops next after Vista). I have worked hard to load all the needed programs on this machine, but it has extreme difficulty with many programs I use. And, 3. Most of the tasks I have to work on are of the variety I dislike... mostly time sensitive paperwork issues that aggravate the hell out of me. Add to this that paper shuffling tasks and recordkeeping are not my strong suits and it further makes the day rough.

I have to figure out a way to combat these feelings. Just stating them for the record here has taken a bit of the edge off so that is a positive.

Perhaps I should just go out an drink a bunch of green beer for lunch as it is St. Patrick's Day? That could enhance my mood for the afternoon? Just a thought.

PipeTobacco

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Interesting Potato Growing Method

With the end of harsh sub-zero weather only a few weeks or months away, I have started to allow myself to think about warm weather, green plants, and possibly even spring. In looking around at various sites, I stumbled across this very interesting idea as a link from Spirit Doings website. The idea is to grow potatoes in a vertical method that increases significantly the yield. I think I might enjoy trying this myself:

Sinfonian's Square Foot Garden: Build As You Grow, Potato Bins

It would be a lot of fun to show people a small potato growing area and then report back the supply I grew.

PipeTobacco

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Beauty And Art

The linked image is of the Shannon Domed Calabash Pipe that I have had my eye on for some time. It is about $75.00 and I am debating the value of purchasing said beast.

To me, the above pipe is akin to a fine sculpture, a thing of beauty and grace. Additionally, it is something that is wholly functional as well. Do you see the beautiful grain in the briar bowl? The curve of the stem?

While I do salivate over this beauty, I am likely NOT going to purchase said. I have plenty of pipes, and really could not easily justify such a purchase, for in reality, my money would be better spent in other avenues such as a donation to a soup kitchen or something similar.

But, I can still think about it and admire its beauty and charms from afar.

PipeTobacco

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Work And Life

Do you know, if I were to talk about work, most of the time I have to mention how taxing and aggravating my job is. Yet, that is REALLY far from the truth. I really feel enriched and enjoy the REAL aspects of my job. I love teaching, I feel fulfilled when I am able to get in front of a classroom and help them to see the beauty of the topics I get to teach them. I love research. I love the hunt for discovery, the planning and execution of creative new experiments. And, I do love service. The vast majority of committees I am on are rewarding and give me a broader perspective of the University, or of my community, or my nation.

Yet, why do I feel so UNHAPPY about work so many days? It is because of the following situations:

1. Interruptions galore - from the members of the Department, from students not during my office hours, and from the phone. I try to combat these by "hiding" in a back office where I can quietly work away, but it is often not very easy to get to work there. My "good" computer is in my main office, as are most of my books and papers that I need.

2. Meetings that are crap - the primary culprit in this arena are the Departmental meetings. I try to combat this by having other meetings I need to go to occur in a way that they overlap a bit with part of the Department meetings to allow me to leave early and by bringing other things for me to work on to be able to ignore the insanity of these meetings. Yet, neither of those things seems enough.

3. Other people's deadlines - that then get foisted onto me as a deadline as well. This occurs with letters of recommendation I need to write for students and others, for meetings with students to fit *their* schedule, and pressures from middle management administrators who set up times and deadlines to make themselves feel important. I am quite at a loss on how to combat these issues at the moment and have had little success avoiding them.

4. Messes - my own messes (in the lab, in the office, in my briefcases, bookbags, backpacks, in my truck, in my yard, in my home, in my den) and the messes of others (in my lab, in the teaching labs, in the lecture halls). It seems that a HUGE share of my time is spent cleaning and organizing papers, items, details, etc into some sort of MANAGEABLE order. Please do not think I am being a Felix Unger (on the right side) who is obsessed about cleaning... for I am actually more akin to Oscar Madison (on the left side) from the 1970s television show "The Odd Couple" which was based upon the Neil Simon play and film by the same name. I am merely trying to get the cyclone messes into some sort of minimal order to allow function. I do not know any way to combat this issue.

5. Lack of Time - There are SO MANY things I WANT to do, but over the last several years, TIME seems to have accelerated and I seem to accomplish less per unit of time. It was only a few years ago when I felt I had time to relax every day, was able to get all the things I wanted to finished, and spend time with my family. Now it seems like I get up at the crack of dawn and rush from deadline to deadline, trying to fit everything in, and often do not really sit down to relax until around 9pm or later every day. I have no clue on how to combat this problem.

So, as you can see, I am a bit mixed up and confused on how to improve my life in the above mentioned. Any helpful advice would be appreciated.

PipeTobacco

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Exercise Day 171

During the last few weeks of emotional strain, there were NUMEROUS times when I almost "fell off the wagon" so-to-speak, and ALMOST did not take my walk. Yet, I can report to you today that my progression remains intact. Today is the 171st day in a row that I did indeed walk my multi-mile walk. Even though in comparison to the hardships I have had to deal with, my walking was indeed inconsequential, I am still very glad I have stuck with it.

I *know* for me, that if I were to take a single day off, and have a break in that progression of the numbers upward (I would have to start over at zero), I would have broken the spell in my mind that keeps me motivated enough to do the walk even when I am hurting emotionally. I think there is a very high probability that if I took off a single day, I would then be likely to start taking off two or three days a week and within a matter of weeks I would not be walking any longer.

If I did not walk, I would revert to my old behaviors and not feel as good physically as I currently do. It is not something I wish to happen.

In an effort to keep me more firmly motivated, I am contemplating one or more of the following endeavors:

1. Preparing to run/walk in a regional 10 km road race.

and/or

2. Beginning a "counting" of regular weight training in the gym.

and/or

3. Planing a "walk around my county" sort of sorjourn over a period of two weeks (it is roughly 130 miles to walk around the entire perimeter of my county) during the Summer.

PipeTobacco

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"And Away We Go, or "I Went""

I was gone for a significant period of time from this blog. The reasons were primarily emotional but a bit of it was also due to work related pressures. The primary emotional pressures stemmed from:

1. The second year date of the passing of my mother. This date always gives me pause and I end up feeling contemplative and melancholy. She was such a wonderful presence in our home the last five years. Me, my wife, and my kids all felt wonderfully blessed to have her with us. And, I do so harshly still feel a hole in my soul because I do not have here here in a physical sense any longer.

2. We have experienced a miscarriage in our family at this time. We are all very sad and devastated about the loss. It is really still a bit too raw emotionally for me to talk about, but I suppose that as time progresses, I will feel more able to talk about this as well.

3. I have had SO MANY relatives and friends die in March that this month always is met with nervousness and discomfort. Just a small sampling of those whom I love who have passed away DURING THE MONTH OF MARCH during my lifetime: my mother, my father, an older cousin who lived with my family and was much like a grandfather to me, two uncles, my major professor from graduate school, and a very close family friend.

So, the above explains at least in a cursory manner what sidelined me for a spell and kept me from writing. But, please know how strongly I value all of you readers, for without your presence, I would never have made it back here. And, I believe that this writing that I do is a very healthy thing for my mind, my soul, and my spirit. I thank you for being here.

PipeTobacco

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Endocrine Disruption in Prawn

One of my favorite research topics related to my own research is the study of endocrine disruption in the environment. Below, I present a report from Biology News Net that reports on possible endocrine disruption in prawn (an animal similar to shrimp) that are bred in captivity.

Just a brief aside, as you can see, I am trying to get myself back on track after being away for quite a spell. It has been a very rough time for me lately. Yet, instead of the too many times before "pull myself up by my bootstraps" post, I thought I would just begin anew with what my plans have been all along. As the week progresses, I will fill you all in on more of the harshnesses that resulted in my lack of posts, but I will not try to have it be the only focus.

The ultimate source for this report is The Queensland University of Technology:

A Queensland University of Technology researcher has filmed hours of prawn "sex tapes" to find out why prawns bred in captivity did not go on to breed well.

Life sciences researcher Gay Marsden spent two months at the Bribie Island Aquaculture Research Centre, run by the Department of Primary Industries, filming what prawns got up to when the sun went down.

"The Australian prawn aquaculture industry depends on black tiger prawns, Penaeus monodon," Ms Marsden said.

"Currently the broodstock that supply the larvae to stock the ponds are captured from the wild.

"Wild-caught prawns spawned millions of eggs, which meant that not many needed to be caught for commercial production, but there was a high risk of disease.

"Viruses can be introduced by wild broodstock, and in high density ponds, crops can be wiped out in days."

Ms Marsden said it is therefore preferable to use captive-bred prawns as broodstock as they can be kept free from the troublesome viruses.

"When prawns are caught from the wild and put into tanks, they have no problem breeding," she said.

"It is a different story for the prawns reared in captivity.

"It was suspected that prawns bred in captivity weren't interested in sex but very little was known about why this was the case, so I undertook the study to try to find out."

Using infrared cameras, Ms Marsden compared the bedroom behaviour of captive-bred prawns with wild prawns and observed combinations of captive-bred prawns mating with wild prawns.

"Males mate with females after the females moult, when they have lost their shells their bodies are soft and can be implanted with sperm," she said.

"But when I looked at the videos of the captive-reared prawns, when the females moulted, the males weren't interested, indicating pheromones were lacking.

"Their non-reproductive behaviour is normal, so they appear healthy in that regard, but there is a problem, the male and females are not attracted to each other.

"I found it was partly the females fault probably for not releasing many pheromones, but there was also something wrong with the males, they weren't very receptive to what pheromones there were."

Ms Marsden said that for an animal that had a brain the size of a pin head, prawns were surprisingly complex.

"From my research, we've got leads for improved nutrition and have also carried out some trials looking at the effect of different hormones on the prawn reproduction," she said.

"Their endocrine system is not functioning normally and further research is needed to find out why that is."

Ms Marsden said while prawns were best eaten at smaller sizes, the black tiger prawn broodstock grew to about 23cm long. They are found off the Australian east coast and in South East Asia.

Endocrine disrupting compounds are a sadly all too common occurrence in our world. We need to adopt policies to better regulate and/or eliminate these sorts of pollutants.

PipeTobacco

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Numbers

Today is March 2nd, 2009.

It was two years ago today that my beautiful mother died.

It was two days ago that a beautiful baby was miscarried.

It all seems like too much.

PipeTobacco