The snail gets up
And goes to bed
With very little fuss
-Kobayashi Issa (1763– 1828)
Archives
Aside
Substrate Level Phosphorylation
Several processes occur during normal eukaryotic metabolism to create ATP. During glycolysis (the breaking of sugar) both prokaryotes and eukaryotes use energy from the chemical bonds in the sugar to make ATP by directly transferring phosphates from the substrate molecule to ADP, resulting in ATP. Predictably, this process became known as ‘substrate-level phosphorylation. Both Cell Respiration, occurring in the mitochondria, and the light reactions of photosynthesis, occurring in the chloroplasts, also made ATP, however, no one understood how this occurred as no intermediate substrate molecule bearing the phosphates groups was known.
1978 Nobel Prize in Chemistry winner
The Peter Mitchell, working at his own, privately funded research foundation, tackled this problem and determined that the power to make ATP came from two processes linked indirectly. For his work in this area, Mitchell won the 1978 Nobel Prize in Chemistry “for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory”.
Model diagram of electron transport and H+ translocation across the membrane
Electron flow carries H+ across the membrane
Process#1: One of these processes is the electron transport chain (E.T.C.) during which a high-energy, excited electron is passed down a series of membrane proteins. As the electron is passed, it sometimes pulls hydrogen ions (H+) along and passes them across the membrane (see the cartoon illustration of this model by Mitchell). As a result, this process creates an electrochemical gradient across the membrane with more H+ on one side compared to very few on the other.
Process #2: As we know, these gradients will ‘want’ to resolve themselves and move towards equilibrium (by diffusion). There exists a special channel protein that H+ may pass through from the side of the membrane with a high concentration of these ions to the other.
“Each chemical species (for example, “water molecules”, “sodium ions”, “electrons”, etc.) has an electrochemical potential (a quantity with units of energy) at any given location, which represents how easy or difficult it is to add more of that species to that location. If possible, a species will move from areas with higher electrochemical potential to areas with lower electrochemical potential; in equilibrium, the electrochemical potential will be constant everywhere for each species”
-from the wiki page on electrochemical potential
I prefer to imagine the membrane and ions as a hydroelectric dam with water building up on one side and a relief passage through the dam.
Just as energy is captured when water rushes through the dam, H+ ions coming through the channel protein are used to power an enzymatic subunit that synthesizes ATP.
Sigma-Aldrich provides an excellent animation illustrating how ATP Synthase operates as both a H+ channel and an enzyme making ATP.
A conceptually simple set of experiments provides the evidence supporting this model. Here, an artificial membrane is made incorporating ATP synthase and bacteriorhodopsin. The rhodopsin molecule is capable of transporting H+s across the cell membrane when it is struck by light. Given sufficient supplies of H+ ions, ADP and Pi, ATP will be formed when a light source is present. In the absence of light, no H+ is transported and no ATP is made.
When a H+ carrier molecule that can diffuse through the membrane is introduced, this carrier maintains equal amounts of H+ on both sides of the membrane. Further, even when light is present, H+ is pumped across the membrane and then re diffuses back creating little or no ATP. This is illustrated in a cartoon from Albert’s Essential Cell Biology:
Chemiosmosis defined experimentally
Chemiosmosis and the work of Peter Mitchell
Aside
RadioLab: Source of great conversations
I wasn’t searching for a way to talk about death and the end of life discussions that families must have about it. I was just transporting my son from our home in Paola, KS to his gymnastics class in Lenexa. It’s a thirty minute drive – give or take. Perfect for a good conversation or a couple songs – perfect for a RadioLab Short.
My son is seven and we both like listening to these programs on our drives. I know he’s a little young for much of the material, but it always makes him ask such good questions. It challenges him in his thinking and he gets to see a parent consider and turn over new ideas too.
I wasn’t paying strict attention. I was driving. I was zoning. I was in the audiobook / NPR / Podcast Groove. My eyes on the road, my mind on a walk with the program. We were driving North at about 70 mph and absorbing the program as it pulled us in, bit by bit.
Doctors who would accept given care options if they were in a state of advanced illness
The Bitter End – a short about how doctors and lay people see end of life care through very, VERY different eyes. To be honest, there was nothing very surprising in the discussion on the radio. Despite the fact that I am not a clinician, my viewpoint of end-of-life care was precisely in line with that of most medical professionals that were surveyed in this report.1 But, that’s a completely reasonable consequence of the proximity of my work to the medical field, having many close friends who are physicians -even my wife in a clinician.
The reality is, people who work in and around hospitals and people who’s impression of hospital care is shaped as much or more by real hospitals than those in TV land, have clear, unromantic ideas about what end of life is like. Also, we have seen more and talked about more situations of ‘heroic’ interventions and know what those outcomes look like.
For instance, my aunt had a heroic intervention by a neurosurgeon following her seizure and fall on the stairs that resulted in a severe head injury, best left to its natural conclusion. Instead, I listened to the doc pat himself on the back for his ability to save her life and turn a sudden trauma with a virtual DOA arrival at the hospital into a yearlong struggle with finding her care as she remained in an unresponsive coma. Oh, and I almost forgot, that meant that we had to actively make the decision to withdraw her feeding tube and fluids so she could die slowly over a number of days in the only legal outlet from this terminal condition. So,… thanks, Mr. Surgeon. Good work.
As I said, I was sort of in the zone and not thinking until we came to a stop at a red light and I suddenly remembered my seven-year-old passenger and thought about what we were listening to.
I don’t believe that there is anything wrong with talking about death – even with children. Death comes to us all in time and we all lose parents and friends and other family. Nevertheless, I thought I might want to take a quick exit before the story went too far. But to turn it off, I had to ask if he had been listening (yes) and would he like to talk about what we heard? (also, yes)
I was relieved when he told me that if I was in the hospital and going to die that he would tell the doctors to give me a ‘sleep shot.’ Then he thought about it … and thought about it some more… And then the waterworks started and he was wailing about how I couldn’t even die, nor his mother, nor his grandmother (Oma) – who would mend his blankie?! No. None of us could ever die. And he would tell the doctors to do anything and everything they could to keep us alive for one more day, one more hour, or minute, or second. And when we died, he wanted to die as well.
Are you feeling lucky?
I let him cry a bit and brought him back from the brink with some cuddling in the parking lot of the Chinese restaurant we were headed for. Then we had a nice talk about cognitive dissonance before we drowned our sorrows in wonton soup.
Reference
1. http://www.jhu.edu/jhumag/0601web/study.html
End of Life Care: A RadioLab discussion
Aside
- Counties Declared in Drought Emergency Summer 2012 (4)
It would be easy to forget that we are still in a fairly severe drought in the midwest. Over the summer of 2012 82 counties in Kansas were declared as federal drought emergencies in early July 2012. Just two weeks later governor Sam Brownback declared every county in the state to be in a drought emergency. Each declaration has different meanings as the first allows for federal aid for agriculture and related industries, while the second allowed water to be taken from lakes in state parks to aid the same industries(1,2).
100% of Kansa counties in drought emergency August 2012
This summer the drought was hard to miss. Ponds were down to puddles, crops were failing and getting tilled back into the soil all around, trees were turning autumn colors and dying in July and lawns were dead with the ground dry and cracked.
Personally, I’ve never seen anything like it. Apparently, this was the worst drought in 25 years, if not more. Not long after, the East coast was getting hit by freakishly early winter storms and ‘superstore Sandy’. (I got regular updates from my family, who all live in the mid-Atlantic region).
Now, on the last days of December, the drought feels like a thing of the past, however, we are still in severe conditions here in the Midwest (I live in Kansas). I heard yesterday on NPR that Kansas is still 17″ below normal rainfall, and a quick look to the NOAA shows that the entire state is somewhere between ‘severe’ and ‘exceptional’ conditions (3).
With luck, I will be shoveling endlessly this winter and we can recover somewhat by spring.
I want to apologize, I haven’t been posting much lately because my family has been away and I have spent most of every day outside working on the shop from first light until dark and then collapsed exhausted inside.
I did have some time while waiting for my wife’s car in the shop yesterday to get a simple children’s book I wrote for/with my son put together as an iBook. It was submitted yesterday and will likely be available for free download sometime this coming week. I’ll post again when that’s available. (Don’t expect much though, the original was a hand-drawn mini book that I redrew using Fifty Three, Inc.’s ‘Paper’ App and an artist’s stylus… and I’m not that much of an artist)
1. http://www.ksda.gov/news/id/472
1. http://blogs.kansas.com/weather/2012/07/26/kansas-governor-declares-entire-state-is-in-drought-emergency/
3.http://www.crh.noaa.gov/eax/?n=drought
4. http://www.kwo.org/reports_publications/Drought.htm
Aside
In class this week we will be continuing our discussion of genetics / inheritance by completing chapter 23. We will also take a timeout to watch a short clip from a movie I enjoy that ties into the topic of probability that we will discuss in association with the coin toss lab (in your handbook).
We will then finish class by talking about Your Inner Fish, the ‘Making Scents’ chapter.
Altogether, this should put us on schedule to have a quiz on inheritance as it was known by Mendel on Thursday.
Aside
The Human Microbiome Project is an NIH-sponsored initiative with the goal of identifying all of the many kinds of micro-organisms that we harbor in our bodies as healthy individuals. This is an interesting project for a number of reasons. First and foremost, because we have long assumed that micro-organisms are present only when we are sick – not healthy. Also, what we learn from this project can have a great impact on how we use antibiotics to treat many of the infections we get that do make us ill (often demanding them as patients even when they will do no good as when we have a viral infection like flu or the common cold). Lastly, we are now learning that alterations in the microbiome of our gut or elsewhere may contribute to more subtle changes in our health, like the incidence of allergy, asthma or obesity.
There have been a number of articles on this topic since the publication, in June 2012, a reference database of what constitutes a healthy microbial population. An excellent thorough examination of these data and their application was published in The New Yorker’s Annals of Science column by Michael Specter, ‘Germs are Us, Bacteria make us sick? Do they also keep us alive?’ Therein, Mr. Specter examines the impact of many modern developments that may be tweaking the population of microbiota that we harbor (especially in our gut), from the use of antibiotics, to the fiber content of the food we eat, to our obsession with cleanliness.
H. pylori
Amongst the scientists doing work that Mr. Specter refers to is Dr. Martin Blaser of New York University’s Langone Medical Center. Much of Dr. Blaser’s work has focused on the role of Helobacter pylori in health and disease. This organism is of special interest because a number of years ago this very organism was identified as causing gastric ulcers. In fact, I use this year after year in my own class as an example of how Koch’s Postulates were applied to pinpoint the cause of these ulcers. In those experiments it was shown that many ulcers have populations of H. pylori growing in them and that these organisms can be transplanted into the gut of a healthy patient and cause the same disease. Further, treatment that kills H. pylori results in amelioration of the ulcers.
Nevertheless, Dr. Blaser’s work does not focus on the role of H. pylori in disease, but rather on its role in maintaining the health of the organism. He, and others, have shown that ridding the body of H. pylori may result in an increased incidence of gastric reflux, asthma and obesity. This relationship is discussed in a short article in The New York Times from 2011. It may not be that H. pylori itself is responsible for all of these conditions, but perhaps other organisms that are eliminated by the same drugs that kill H. pylori contribute to these conditions.
Obviously, there is a lot going on within our bodies and a holistic view of how our actions impact a wide variety of systems may be required in order to successfully design treatments that target the ill-effects of some micro-organisms while preserving the health-promoting effects of others.
I’m definitely going to put some more work into researching this topic so I can incorporate a discussion of it in my microbiology class next semester, so don’t be surprised if you read more about this here in the future.
The Human Microbiome Project at Work
Aside
A static view of the tree of life
Onezoom.org is an effort o display all of life and its relationship with one another in a single ‘zoomable’ phylogenetic tree. Currently one the mammalian branch of this tree is available, but it is still extraordinarily interesting and gives an idea of the grand scope of the project. Here’s an introductory video showing the intent of the project and why the organizers developed it in the way that they did.
Here’s a link to the site itself where you can try out the viewer. — By the way, +1 point on the upcoming chapter 5 quiz for any of my students who try this out and can email me a screenshot of where humans fit into this tree. I realize this requires you to go to the site, try out the viewer, find humans AND work out a way to visually document that -but there it is.
I would like to thank nothinginbiology.org for pointing me toward this resource. I tried to reblog their post, but I ran into some silly technical problems and found it easier just to write up something myself.
OneZoom
Aside
Scientific method as a lens to view the world
Science has a problem in telling its stories to the world. The problem stems from the way that science is done and the way its discoveries are published in academic journals not known for their mass appeal. In science, seeing something happen once or hearing about an occurrence might lead one to get in the lab and ask a question, but it is never itself acceptable as an answer. Instead, multiple repetitions of an experimental question are asked until consistent results are found under controlled conditions. Compare this to watching the news or reading the paper and you’ll find a drastic difference. Mass media loves the anecdote of ‘one family’s story’ or ‘what happened to my kid.’ Stories appeal to our natural tendency to relate to people and to incorporate the underlying morals or lessons into our broader worldview. He-said-she-said arguments are presented as fair and balanced even when balance is unjustified. With this in mind, consider this story of how the birth of the scientific method changed the world we live in.
The events of the late 15th and early 16th centuries ushered in a new age. Not just in the discovery of new land to be conquered and populated by western civilizations, but also in the way westerners saw the world and their place in it. Suddenly there was half a globe of terra incognita. As Columbus revolutionized our geography, Copernicus and Galileo revolutionized astronomy. But what was good for cartographers and astronomers wasn’t so good for the royalty and the church, who had been comfortably enjoying in the status quo.
At that time, the vast majority of people were ruled by the very few who held their power by divine right. What they said was both fact and law and any who differed in opinion did so at their own peril as autocracy seldom views challenge or change as good.
But cracks were beginning to show.
Between the discovery of the west and the mounting evidence for heliocentricity, came the greatest schism the Christian church has ever seen, hammered home when Luther nailed his 95 theses to the church door in Wittenberg, Germany 1517. Within a century a new world was discovered, the earth was shifted from the center of the universe to a body orbiting the sun and even God’s own voice on earth was being challenged due to a poor financial decision granting the sale of indulgences. How unfortunate for those in power that the printing press, which Johannes Gutenburg had introduced a half century earlier, made it so easy for this news to circulate around the globe amongst a newly literate population.
By the middle 17th century, Bacon and Descartes were formalizing the rules of logic and, more specifically, of scientific inquiry. Their texts, Novum Organon and Discourse on Method display a new desire for evidence-based reasoning rather than simply accepting facts ad hominem – even in cases where the hominemis the Pope himself. Bacon wrote, “The logic now in use serves rather to fix and give stability to the errors which have their foundation in commonly received notions than to help the search after truth. So it does more harm than good.” That is, too much effort is being spent defending what we already think is true rather than just following what the data tells us. This is exemplified by Ptolemy’s
How Ptolemy saw the solar system
complex system of interlocking circles and the complex movements they require in order to explain the wanderings of the planets in the night sky. An excellent demonstration of this backwards logic can be found at http://people.highline.edu/iglozman/classes/astronotes/retrograde.htm
With the upset in worldview brought by the renaissance and its new rigor for asking scientific questions along with a few intervening centuries, one would think that we would be more discerning in our beliefs today. We should be open to new ideas that challenge accepted dogma, and be in possession of tools to discriminate between unfounded speculation and well-supported theories.
Or, perhaps not.
In many ways, we are just as easily swayed by ad hominem arguments, faulty logic and satisfaction with the status quo as we were seven hundred years ago. But it’s not entirely our fault. We’re not built to think critically, rather, we make quick judgments based on what we see in front of us. The ability to make split second decisions were likely required to save our skin in the time of Hobbes’ “state of nature.” While labored, methodical reasoning would reason us right into the lion’s mouth. The difference today is that we are vastly more educated than our forbearers, possibly smarter -if rising IQ scores can be taken at face value- and, frankly, we do have the time to practice methodical reasoning. Rarely do we need to make life saving fight or flight decisions in modern life.
Science has taught us that the universe may not be as we see it. In fact, our senses are fooled all the time. Sticks don’t bend when we put them in water, a continuous tone may appear to change pitch as the source approaches or recedes from the observer and quantum mechanics tell us that all the matter of the world is nothing like what it appears to be. Our senses tell a variety of lies to us, but nature does reveal her laws with careful study.
Understanding scientific method is teaching oneself to remain impartial to results of experiments, to ensure that the tests applied are rigorously designed to disprove – rather than support – your hypothesis, and to rely on the power of statistics to interpret your results rather than being swayed by anecdote or a desire to see a predetermined outcome. None of this comes easily. As I said above, we are a storytelling people, stories are the lenses through which we view the world. It’s a lot easier and exciting to believe an anecdote than it is to understand the truth. But it’s often worth the effort and sometimes there might be an interesting story behind the science too.
An old essay I wrote about the scientific method
Aside
Who’s doing what here and why in this famous painting depicting one of the preludes to a major battle that turned the tide of the war in favor of the Continental Army?
Insight into an Extra Credit Question
Aside
Cell Division is an essential part of life. However, this means different things to different cells. For single-celled organisms cell division is reproduction – one mother cell divides into two daughter cells. If these single-celled organisms are prokaryotic, then this division happens by the relatively simple process of binary fission. If the organism is eukaryotic, division occurs by a more structured process of mitosis.
Regardless of the differences between these organisms, cell division consists of three core components:
- Duplication of DNA
- Segregation of DNA (into areas that will become the new cells)
- Cytokinesis
In Prokaryotes, this describes the cellular events perfectly. The circular DNA (arguably a chromosome) is duplicated, the two copies of the DNA goes to opposite sides of the ce
ll and cytokinesis divides the cell in half along the midline.
An illustration of a number of bacterial cells undergoing binary fission:
The entire process is outlined below:
In eukaryotes, the same basic process occurs, but because of the differences in how DNA is organized and localized (in a nucleus), differences emerge.
The basic form of eukaryotic cell division is called mitosis. In single celled organisms this process functions as an asexual form of replication, while in multicellular eukaryotes, this form of division serves to add to the cell number (i.e. growth / healing).
Mitosis is actually the division of the nucleus and DNA, this process is accompanied by the division of the cell itself, cytokinesis.
There are four phases of mitosis:
- Prophase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis overlaps somewhat with Telophase, but continues on afterwards to complete cell division.
Each stage of Mitosis is defined by a number of events describing the organization of the DNA, the state of the nuclear membrane and the development of mitotic spindles that maneuver the chromosomes within the cell. I won’t describe these here as this can be found in any number of other sources.
What I will discuss is the pattern of chromosome number, DNA copy number and the chromosome number.
The chromosome number is referred to as ‘n’.
The DNA copy number is referred to as ‘c’.
Humans have an n number of 23. What this number tells you is how many pairs of homologous chromosomes an organism has.* This immediately begs the question, ‘what’s a homologous chromosome?”
Homologous chromosomes are those that have the same genes – that is, they code for the same traits even if they do not have exactly the same versions of these genes on each chromosome. For each of the 23 different kinds of chromosomes humans have, each person gets one copy from their mom and one from their dad. So these 23 pairs of chromosomes are 23 pairs of homologous chromosomes.
This 23 number we keep talking about is the n number in humans. Each species n number may be different, but all the members of that species have the same n number. Further, the n number does not change at any time during the cell’s life
Because we have one chromosome from each of our parents in every one of the cells of our body we are diploid organisms (from the Latin, di – meaning and two ploid – well, ‘ploid’ doesn’t really come from Latin)
All the cells in our body are diploid – except the gametes (sex cells). These cells are formed by a special kind of cell division called meiosis. This type of division is very similar to mitosis, except that it consists of two separate rounds of division and the resulting sex cells have only one of each chromosome type and are therefore called haploid (think ‘half’)
Cells of the body are 2n = diploid.
Sex cells are n = haploid.
This leaves the c number…
The easiest way to determine the c number is to simply count the number of chromatids for each type of chromosome. Consider the cells below. On the left is a cell in G1 phase of the cell cycle. Then the cell goes through S phase where DNA replication occurs and looks like the cell on the right.
Note that the n number does not change, but the c number doubles when the number of chromatids doubles.
* It’s important to note here that not all organisms have similar patterns of chromosome arrangements as we humans do. In this essay I am referring to humans and organisms that handle their DNA as we do.
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