A Dynamic System of Accetylating and Deaccetylating Factors Has Effects on Transcription

Specific sequences in DNA recruit transcription factors, called activators and repessors, coactivators and corepressors. In order for DNA to be transcribed and expressed, the chromatin needs to be decondensed (accetylated) to allow for there to be enough space for these transcription factors to bind. For a transcription factor to bind, it binds to a histone acetyl-transferase, which unfolds the chromatin.

However, either side of the recruitment position has deacetylating enzymes. This creates a battle of kinetics and equilibrium shifts, where the two forces of accetylation and deacetylation are competing to determine the outcome of whether or not the transcription factor can bind to the region. Also, the success of transcription depends on how long the transcription factor can bind. If the factor is easily displaced, transcription cannot occur.

It is possible for heterochromatin to have an activator bind to a promoter, but it is less probable because of reaction kinetics. In the lab, if decondensation is required for a highly deaccetylated region, viral components are used to induce this process.

There are other chromatin modifications, which contribute to a histone code. The histones are modified in different ways to alter the charge and the overall surface of the protein, which effects the binding properties. Common alterations include phosphorylation, mono-ubiquitination, and methylation.

Phosphorylation, mono-ubiquitination, and methylation lead to either activation or repression of the gene depending on location of the modification. If we examine more closely the effects of methylation in particular, the properties of the three methyl groups bound to the histone cause the amine function to be blocked, and the positive charge to be maintained. This, in turn, blocks acetylation, which means the chromatin in that region will be condensed, and it is unlikely transcription will occurs.

Each of the histone modification reactions is reversible and carried out by enzymes.

In addition to the above methods to modify chromatin structure, chromatin remodeling mediated by chromatin remodeling complexes also is possible. The complexes detach the strong interactions of the histones with the DNA, in a way that does not completely remove them, but makes the DNA more accessible.

The process of initiating transcription is dynamically controlled by access to the DNA regions and how tightly the chromatin is bound.

Note:

Recall that acetylation is when the lysine residues in histones are bound to an acetyl group, making the positive amino acid neutral. This prevents the interaction of the histones with the negative phosphate backbone of the DNA, and the chromatin is decondensed, allowing easier access for transcription factors to bind, and gene expression to take place. On the other hand, deaccetylated histones do not have the acetyl group bound, and the lysine residues maintain their positive charge and are attracted to the phosphate backbone of the DNA, causing the chromatin to be condensed, and reducing expression.

Gastrointestinal Tract Poetry

One of the most charming professors at McGill University is Dr. Ann Wechsler, with her pleasant manner, and lectures full of not only facts, but also encouragement. Last semester, she coordinated the first introductory physiology class, and wrote many poems that eloquently and concisely summarized concepts. Truly, she is a gem of an instructor, and I have heard nothing but compliments from other students describing her teaching.

So, naturally, when she returned to the second semester of introductory physiology, I asked her if there would be any poems that day. She informed me that I could write a poem for the Wednesday lecture summarizing the Monday lecture content. And so, honoured, I did.

If you look into the deep past of this blog, you will find some ancient poetry written recreationally for high school and some university classes, mainly to amuse my peers. Lately, I haven't been writing much academic poetry, as the content is more technical, so double entendres become more difficult to incorporate. However, I did my best, and I hope you will enjoy reading this poem as much as I enjoyed writing it!

To absorb information of the Gastrointestinal Tract

We must digest thoroughly for maximum impact!

It developed from a tube passing straight through

To a larger structure with differentiated tissue.

At four point five meters it certainly isn’t short,

With surface area extending an entire tennis court.

The serosa is a layer tough, but thin in style,

Where as the muscularis externa is versatile,

With fibers either parallel or angled to the right,

And skeletal and smooth; then the submucosa site,

Which covered in loose connective tissue and nerves,

Underneath the mucosae with three layers deserves

To be mentioned, with muscularis mucosae smoothly designed

And lamina propria with loose connective tissue defined.

And lastly the business end, the single epithelial layer

With its endocrine and exocrine functions is a key player.

But what about the major functions of the GIT?

We have secretion, absorption, and motility!

The saying to think with your stomach is correct,

As the enteric enervation certainly does connect

An assemble of elements for a complete reflex arc:

Many action potentials together with algebraic spark.

Both autonomic systems together regulate

The enteric nerves and their cumulative fate,

As ACh excites a neuron’s respective role

Be it to activate or inhibit the signal as a whole;

Where as NA does the opposite, the role it prohibits

And excites enteric neuron which ACh inhibits.

The enteric neurons that inhibit release NANC,

And those that release ACh are excitatory.

This signals either a secretory or smooth muscle cell

And if this seems rather complicated – well,

I admit this poem summarizes quite a lot,

Because after all, it serves as food for thought! 

It's All Greek to Me

When I spoke to an advisor about my schedule for the new semester, she looked over my selected courses, and verified that yes, indeed they were required for my 2nd year of my physiology program, and they would stand me in good stead for completing my degree. However, when the advisor came to the mysterious course code of CLAS220-D2-001, there was an audible sigh from her side of the desk. I braced myself, as I knew the inevitable was coming.

"Why Ancient Greek?" she asked. 

This question has been posed from my colleagues in my physiology lecture, my mystified parents, and any advisor I set sights on the McGill campus. Clearly, Ancient Greek is not a prerequisite for any upper level physiology course, and the vocabulary I learn from hoplites to the marvellous verb "to be a choral dancer," does not always directly relate to origins of scientific nomenclature. But, over this past year I have heard many different stories from students in my classes, about their electives. And maybe the question should be changed to: 

"Why East Asian Cultural Studies?"

"Why French?"

"Why Art of Listening?"

"Why Greek Mythology?" 

"Why Gifted Students?" 

"Why Linguistics?" 

And then, to form a general over-arching question of the above: 

"Why take an elective that does not directly relate to the course requirements to your degree? Especially an Arts Elective?"

In response:

Why bother to attend a university if you are not inquisitive and love to learn? Why should your interests be limited to your degree? Are you not a human being and above all a human being before you are a developing scientist? Do not the different disciplines work together to create a cohesive education that enhances the human experience? 

To further answer the question, "Why Ancient Greek?" and to encourage other science undergraduates to explore a minor that will be enjoyable and complement their core courses, I have included several reasons below from my classes this year in Introductory Ancient Greek as well as last year's elective Introductory Latin. 

1) Smaller Class Sizes 

The undergraduate science large class sizes of first and second year with 600 people are intimidating. Even if you sit with the same people everyday, it is difficult to hold conversations, let alone approach the professor. If you participate in lecture, it is not practical for everyone be active every class, otherwise the hour long lecture would be a continuous stream of questions punctuated by a 5 minute theory section by the professor. The feeling of anonymity is high. 

In both of my Ancient Greek and Latin classes, the professor knew my name by the end of the first lecture, and I met at least three people around me. Immediately, the feeling in the class is more intimate. From each of the quizzes, the professor is well-aware of the common mistakes of each of the 20 students, and can direct the lecture to address your needs. Also, many times the professor notices your mood each class. He/she may comment that a particular student looks particularly tired that day, or if a student does usually poorly on a quiz, may ask after the student's health and schedule from that week. This type of concern has not happened only to me, but to many of my other classmates. The relationship between the classics professor and student on a class by class basis is more nurturing than even with the best professor in an introductory course in the sciences. 

2) Communicative Skills and Group Work

Arguably, in science courses, we obtain practice communicating with different lab partners for each experiment of the semester. However, this type of job is more qualitative as it primarily involves measurements, task distribution, and results interpretation. In a classical language class, much time is spent in groups translating texts. Not only do you gain an appreciation for the differences between english and ancient greek/latin, and how to express oneself more concisely, but also the dialogue involves collaboration between parties about how best to translate the passage. The flavouring and nuances of the translation leads to better knowledge of how to communicate using one's primary language, as well as the second language of study. As a group you become aware of your strengths in both languages as well as your weakness, and you are able to consult the group "expert on clauses" or the group "expert on verb forms" as each part of the sentence occurs. (Note that neither latin or ancient greek requires the student to be able to speak the language, merely read and write it, as the courses are translation driven.) 

3) Appreciation of the Evolution of Language and the Human Mind

The comparison between latin/ancient greek and english reveals the difference between their respective syntax and vocabulary. Since nouns decline in both greek and latin (the noun changes form based on its grammatical role, such as subject or direct object, in a sentence), this shows a greater precision than english. The literary devices that can be used from different grammatical forms, suggests variation in how human beings were thinking during that point in history from today's world. Also, the composition of language reflects the wonder of the human brain, and how it can innately create such culturally varied methods of communication. 

4) Occasional References to Science Courses

Yes, as my science friends like to joke, at least I can recognize every greek letter that appears in our formulae! But beyond this, it can be a memorization tool when the odd vocabulary word overlaps from a classical language class to a science course. The word that comes most readily to mind was introduced in physical chemistry, endergonic and exergonic, where ergos in Ancient Greek means work. More obviously, perhaps, is perimeter, with the prefix peri meaning through. To be a little more complex we have the word paragraph, with para as the Ancient Greek prefix for beside, and graph from the verb grapho, to write. And of course, to be obscure, the ambulocetus, from the latin verb ambulo , to walk. 

the ambulocetus, in case you were curious

5) It Makes a Great Conversation Starter

To my nonscientific family and friends, if I tell them my courses from last semester, they fondly tell me they sound all the same. "Organic chemistry, physical chemistry, molecular biology, physiology" and  they do have a poetic ring together in a list. But Ancient Greek or Latin? Everyone remembers it and wants to talk to you about it. I'm not sure entirely why this is, but the nonscientific crowd tells me that it is cool. I think the science courses make you cooler, but whatever, somehow the general public seems to relate to dead languages more than DNA. Go figure. 

6) The Professor Will Never Ask "Why Ancient Greek?" 

Out of all of the people who deal with you about taking a classical language, the one person who will not question your motives and you is your biggest supporter (from my experience) is actually your professor. When I was having a hard time with organic chemistry last semester, I ranted to my Ancient Greek Professor about my frustration, and she told me, "When I took organic chemistry, it was my least favourite course. But suddenly it all started to make sense, and it became my favourite." 

Now, I was flabbergasted. If there was anyone anti-organic chem, I expected them to be my Ancient Greek Professor, but that someone who was not using the course could still remember it to be worthwhile and to have provided a reward of joy out of the initial struggle - well! These words inspired me more than my organic chemistry professor ever could have! (Although my organic chemistry professor from last term is my role model and when I grow up I would like to be just like her, minus studying chemistry!) And, I am happy to say that my Greek Professor was right in her prediction, and by the end, organic chemistry and I did manage to get along quite nicely too. 

Now, after a long-winded justification, I hope that I have provided an explanation for those who question why science undergraduates take arts courses, and why electives are an integral part of a good university education. 

If you are wondering whether one of these courses is right for you, feel free to contact me. I do however, recommend taking Latin first as it doesn't have a different alphabet and accents to grapple with, and so it allows you to get a better idea of the grammar and syntax. 

Picturing Entropy: Some Examples

The first law of thermodynamics considers interpretations of the law of conservation of energy and how it applies to the system (the reaction under consideration). The second law, however, is interested in the measurement of randomness in a system, the entropy. Before we get down to the nitty-gritty on what that actually means, let's examine some ways in which entropy influences the world around us.

Example 1: Cup of Tea

Say you add an ice cube to your cup of tea. Aside from the wonderful crackling noise the ice cube makes as it melting, what is really going on? First of the enthalpy of the reaction is increasing as the ice cube requires heat to melt. And then, the entropy is also increasing.

Why? Well, in a solid the molecules have less degrees of rotation, as they solely vibrate in a dense structure, but when they melt to become liquid water, the molecules can move around and slide past one another, which is why if you tip over your tea it will spill all over the floor and will make the mess that it does. These further degrees of freedom increase the amount of randomness in the system. And hence, liquids have greater entropy than solids.

Now, let's consider the steam coming off of your tea cup. As you may have anticipated, gases of a substance have even higher entropy than liquids, because the molecules have greater degrees of freedom than liquids.

So in summary: $$entropy_{solid} < entropy_{liquid} < < entropy_{gas}$$
More degrees of freedom = more entropy

Example 2: Denaturing DNA

 Denaturing DNA = breaking DNA from its classic double helix shape into two separate strands.

 Often in the laboratory denaturation of DNA is done in a test tube by increasing the temperature so that the hydrogen bonds that connect the bases (A,T,G,C) break. This is an endothermic process as it requires input of energy, high temperature and results in something with more entropy (2 strands instead of 1).

Denaturing DNA is also a reversible process, so if you decrease the temperature, the strands will re-anneal to the double-stranded helix structure. This can be investigated more clearly by checking out the Gibb's Free Energy equation $G=H-TS$, which I will discuss in a later post.

 Basically, the take home message is that for any reaction, there is a dialogue between the favourable enthalpy and favourable entropy conditions, which will determine whether the reaction is spontaneous or not.

In example 1 with the tea cup, the ice melting and the steam rising, was all spontaneous at room temperature. However, in example 2, this is not as clear. The reaction is temperature dependent, as temperature is the factor that mediates the relationship between the enthalpy and entropy of the reaction.

 But now you are probably wondering: what are the favourable enthalpy and favourable entropy conditions for a reaction to occur spontaneously? Fair enough.

 For a reaction to occur spontaneously, the it prefers to have negative enthalpy, which is an exothermic process (releases heat into the environment).

 "Okay," you say, "But what if I have a giant stick of dynamite in my hands? That releases a lot of heat because it explodes. So why isn't this reaction spontaneous? Clearly it is an exothermic reaction."

Good point. Recall a potential energy diagram for an exothermic process. Some reactions are required to overcome their activation energy for the reactants to turn into the products. Here is a quick 30 second video to trigger your memory if you have forgotten this concept. Activation Energy Definition So in the case of dynamite, it will not spontaneously combust because it requires a certain input of energy - the spark to ignite it - to blow up and overcome its activation energy.

 So, we've covered the spontaneous conditions for enthalpy, but what about entropy? The system is favours states of greater disorder, so the entropy increases positively. A way representing this formally is defining our system (because we can take a system to be as small or as big as we like, as we are the ones who define it) as the universe. Since the universe is an isolated system, we know that $$\Delta{S}_{universe}\geq{0}$$

 Now, this explains why certain reactions with respect to a smaller system can occur at all. As long as the $\Delta{S}_{universe}$ remains positive, which it will because of the massive size of the system, a small negative blip where $\Delta{S}_{system}\leq{0}$, will simply not matter as it is insignificant in the grand scheme of things. We represent this by $$\Delta{S}_{universe}+\Delta{S}_{system}\geq{0}$$ or $$\Delta{S}_{system}+\Delta{S}_{surroundings}\geq{0}$$

 Also, note that a reversible process is defined by $$\Delta{S}_{system}=-\Delta{S}_{surroundings}$$

 All right, this leads us to example 3.

 Example 3: An Endothermic Reaction

 $$\text{N}_2\text{O}_4\longrightarrow 2\text{NO}_2$$

 So what is happening here? Dinitrogen dioxide on the left hand side of the equation is reacting to become the product nitrogen monoxide. The key thing to notice is that there is only 1 mole of reactant to 2 moles of products, so even though this reaction absorbs energy and is endothermic, and hence should be unfavourable, the positive increase in entropy (more products than reactants, therefore more disorder) favours the reaction to proceed. In this case, the drive of the entropy overcomes the enthalpy of the reaction.

In the next post I will discuss a statistical representation of entropy, so stay tuned! :)

An Introduction to Entropy

What is entropy? A measure of disorder can seem abstract and somewhat difficult to envision at times. Can I really blame the state of my apartment with unwashed dishes and dirty laundry strewn on the floor on its agency - or does this have to do more with the subjective nature of personality traits? Can one really measure quantitively disorder when colloquially we refer to it in quantitative terms?

I am very fond of the topic of entropy. In high school, I used to tell horror stories about the eventual heat death of the universe ad naseum. Eventually all of the particles would exist in a solid, perfect crystal state, where no energy could rescue them from their eternal plight.

My musician father was fascinated by entropy while listening to CBC radio program Ideas. Many a skype conversation, he will pounce the topic upon me, and question continuously its definition and properties. Once we devised a system of cells in the human body, existing under ideal conditions (eg: no negative effects of the external environment such as a blow to some tissue, or disease), with only the natural aging process as a factor. Applying the statistical explanation of entropy, we were able to determine it was statically unlikely for all of the cells in an common region of the body to spontaneously die, when otherwise undisturbed.

Walking one evening with a someone special, in the crisp fall Montréal air, we discussed how if you have an empty chamber attached to a flask filled with particles of gas, and opened the flask to the empty chamber, the gas particles would distribute themselves so they filled every state in the chamber. The movement of our postulated system of order to one of disorder mirrored that of the Big Bang. We found it disturbing that the transition from order to disorder was mediated by an external event of the person opening the stopcock. Does this part of the analogy translate over to the scenario of the Big Bang as well or not? Where did the initial stimulus for the start of the universe come from?

Entropy can lead to interesting conversations with people of all different backgrounds, and also contribute to an enhanced understanding of the behaviour of the universe. For these reasons, I am going to develop the concept of entropy over a series of posts, discussing both statistical and thermodynamic interpretations of entropy, and employing both qualitative and quantitative means throughout my explanations.

These posts will be dedicated to my dad because I have always promised to explain entropy throughly to him, but we never have sat down properly to discuss it.

Ideal Gases: Reversible Adiabatic Process

For a reversible adiabatic process, the system is moving between two different isotherms, so the temperature is changing. Also, the both volume and pressure are changing. So $P_1V_1T_1 \rightarrow P_2V_2T_2$.

The work done in an adiabatic process is less than that of an isothermal process, as an isothermal process is the maximum work possible to be done on the system. $w_{adiabatic} < w_{isothermal}$

For a reversible adiabatic process, there is no heat transfer to the system by definition, thus $q=0$. Since $\Delta{U}=q+w$, then $\Delta{U}=w=-PdV$.

For the following derivation, to make our lives a bit easier, we are going to consider the case where $n=1$. $$dU=-PdV$$ $$C_vdT=-PdV$$ $$C_vdT+PdV=0$$ $$C_vdT+RTdV/V=0$$ $$\text{as } P=RT/V$$ $$\text{divide equation by } T$$ $$C_vdT/T+RT/TdV/V=0/T$$ $$C_vdT/T+RdV/V=0$$ $$C_v\int_{T_1}^{T_2}dT/T+R\int_{V_1}^{V_2}dV/V=0$$ $$C_vln(T_2/T_1)+Rln(V_2/V_1)=0$$ $$\text{recall that }R=C_p-C_v$$ $$\text{divide by }C_v$$ $$C_v/C_vln(T_2/T_1)+(C_p-C_v)/C_vln(V_2/V_1)=0$$ $$ln(T_2/T_1)+(C_p/C_v+1)ln(V_2/V_1)=0$$ $$\text{let } C_p/C_v =\gamma$$ $$ln(T_2/T_1)+ln(V_2/V_1)^{\gamma-1}=0$$ $$ln(T_2/T_1)=ln(V_1/V_2)^{\gamma-1}$$ $$T_2/T_1=(V_1/V_2)^{\gamma-1}$$ $$\text{since } PV=RT$$ $$(P_2V_2)/(P_1V_1)=(V_1/V_2)^{\gamma-1}$$ $$P_2/P_1=(V_1/V_2)^{\gamma-1}(V_1/V_2)$$ $$P_2/P_1=(V_1/V_2)^{\gamma}$$ $$P_1V_1^{\gamma}=P_2V_2^{\gamma} \text{ where } \gamma = C_p/C_v$$ 

To check our work, we can see if this applies to the ideal gas law. $$P_1V_1^{\gamma}=P_2V_2^{\gamma}$$ $$PV^{\gamma}=RTV^{\gamma}/V$$ $$PV^{\gamma}=RTV^{\gamma-1}$$ $$PV^{\gamma}/V^{\gamma}=RTV^{\gamma-1}/V^{\gamma}$$ $$P=RT/V$$ The gamma term can also be related to the number of degrees of freedom,$f$, in a gas. $$\gamma = C_p/C_v = \Delta{H}/\Delta{U}=(f+2)R/fR= (f+2)/f$$

To check out $\Delta{H}$, the entropy, we consider $$\Delta{H}=\Delta{U}+\Delta{PV}=w+q+\Delta{PV}=w+R\Delta{T}$$ $$\Delta{H}=C_v\Delta{T}+R\Delta{T}$$ $$\Delta{H}=(C_v+R)\Delta{T}$$ $$\Delta{H}=C_p\Delta{T}$$

In summary:
$$q=0$$ $$\Delta{U}=w=-PdV$$ $$\Delta{H}=C_p\Delta{T}$$ $$P_1V_1^{\gamma}=P_2V_2^{\gamma} \text{ where } \gamma = C_p/C_v$$

Ideal Gases: Reversible Isothermal Process

Consider system with an ideal frictionless piston to apply and reduce pressure and change the volume. Recall that for an isothermal process that is reversible, the $P_{gas}=P_{ext}$. In this case the work in = heat out. Also, there is no net change in both $\Delta{U}$ and $\Delta{H}$, because the process occurs along the same isotherm, so $\Delta{T}=0$, as $T_1=T_2$.

 Therefore (a bit redundant, but we'll show the equations anyway):
 $$\Delta{U}=C_v(T_2-T_1)=0$$ $$\Delta{H}=C_p(T_2-T_1)=0$$

 Recall, the equation of work of an ideal gas $$w=RTln(V_1/V_2)$$

 Since the heat out is equal to the work in, the heat is given by $$q=-w=-RTln(V_1/V_2)=RTln(V_2/V_1)$$

 Note about the Concentration:

 When the number of moles are not equal to one, we cannot ignore the $n$ term. So when have some $P_1=n_1/V_1RT=C_1RT$ and $P_2=n_2/V_2RT=C_2RT$ where $C$ is the concentration.

Therefore, the ideal gas equation for work can also be expressed by $$w=nRTln(V_1/V_2)=NRTln(P_2/P_1)\text{ as } P_2/P_1=V_1/V_2$$ and $$w=nRTln(C_2/C_1)$$

 These equations come directly from the definitions of the terms. If they seem a bit confusing, refer to earlier physical chemistry posts on this blog, which can be found via the table of contents. Or if not, check wikipedia or something. :)