The 2012 Nobel Prize in Chemistry

Today the 2012 Nobel Prize in Chemistry was awarded to Robert Lefkowitz and Brian Kobilka for their work on G protein-coupled receptors.

How do signals from outside the cell get transmitted into the cell? It's a question that long plagued scientists and the answer underlies many if not all vital cellular processes. It was thought that there were protein receptors on the surface of the cell that recognized molecules and in the process of this recognition, specific events were triggered inside the cell - the action of the hormone adrenaline, for example. In the 1960's Lefkowitz's lab used radioactive hormones to isolate the receptor responsible for the action of adrenaline - the B2 adrenergic receptor. This initial step of isolating the receptor was key in allowing scientists to characterize the biochemical properties of the protein. Isolation of the protein in an active form was not trivial since the receptor had portions outside the cell, portions in the membrane of the cell, and portions inside the cell - it is a transmembrane protein.

In the 1980's Kobilka joined Lefkowitz's lab and set out trying to isolate the gene encoding the B2 adreneric receptor. He was successful and when they analyzed the gene sequence, they realized there were other similar genes - thereby implicating a gene family. As it turns out, there are many genes that encode these protein receptors, all similar in function, but differing in what external signal they recognize and transmit inside the cell. - smell, light, histamine (think allergies), mood, appetite and sleep (serotonin).

Kobilka left Lefkowitz's lab and established his own research group studying these receptors - especially trying to determine their molecular structure. In the last couple of years, his group succeeded in solving the structure of the B2 adrenergic receptor just as a hormone has bound giving new intricate details on how these important signal is transmitted to the cell.

It is suggested that more than half of all drugs act on this family of G protein-coupled receptors highlighting the importance of understanding exactly how these proteins function and opening doors for the treatment of many disorders.

The 2012 Nobel Prize in Physiology or Medicine

The Nobel Committee announced the awarding of the 2012 Nobel Prize in Physiology or Medicine to Sir John B. Gurdon and Shinya Yamanaka for their work on the reprogramming of mature cells to immature pluripotent cells.

It is rather amazing to think that the variety of different cells within our bodies start from a single cell. Those early cells that have the ability to turn into many different types of cells are called pluripotent stem cells. The cellular differentiation process is relatively well understood. But, is it possible for a mature cell to revert to its immature, pluripotent state, or is cellular differentiation a one-way street?

Fifty years ago Sir John Gurdon performed an experiment to test this idea. He replaced the nucleus of a frog egg with the nucleus of a mature cell from a tadpole intestine. This egg developed into a normal adult frog. After subsequent repetition of the experiment it became clear that the information for cellular differentiation still resided within the mature cell. In fact, cells do have the ability to go backward.

After this discovery, the question became, how does this happen? What are the keys to the underlying mechanism of differentiation? In the early 21st century, Shinya Yamanaka took genes thought to play a role in keeping cells in an immature state and injected them into mature cells in varying combinations looking for combinations that would turn those mature cells into immature cells. He and his colleagues did find a combination that reprogrammed these mature cells and surprisingly, it took only 4 genes to accomplish this remarkable task. They went on to show that these reprogrammed cells could differentiate into many different cell types.

The implications of this work are profound. Gurdon's original observation led to the cloning of mammals - Dolly the Sheep being the first success. The ability to reprogram cells by the introduction of just a few specific genes creates cellular tools that allow us to get a better understanding of the underlying processes, the study of changes in healthy versus diseased cells, and even the potential to use these findings to treat degenerative diseases.

There are many unanswered questions about the potential of these reprogrammed stem cells. Dolly the Sheep only lived 6 years and these genetically reprogrammed stem cells appear to have a propensity to form tumors. However, the two discoveries awarded this year's prize have opened up amazing possibilities.

Twilight moon

Sometimes it is enough to sit on the sidewalk
and stare at the crescent moon
and Venus low in the twilight sky.

Other times it is necessary to capture
the moment and share with a friend
2000 miles away.

Bucket List

1. Drive the PCH from San Diego to the Oregon border and then sail back down to San Diego.
2. See a Sox game at Fenway Park.
3. Sit at Bobby Kennedy's desk in the United States Senate chamber.
4. Watch the sunrise from the summit of Cadillac Mountain in Acadia National Park.
5. Take a humanitarian trip to Africa.
6. Hold my grandchildren in my arms.
7. Fly to Boston for a lobster lunch and be back home in time for dinner.
8. Play All Just to Get to You on stage with Joe Ely and Bruce Springsteen.
9. Climb Mt. Kilimanjaro with Kaj.
10. Watch the sunset on a Hawaiian beach. 
11. See the Macy's Thanksgiving Day parade in person with McKinley.
12. See Les Miserables on Broadway.

The Constitution - Article 1, sec 7

Much of the information in this series is found at The United States Constitution Online. I highly recommend this site for further exploration of the meaning of our Constitution and give it up front credit for many of the ideas written here.

Section 7 All bills for raising Revenue shall originate in the House of Representatives; but the Senate may propose or concur with Amendments as on other Bills. Every Bill which shall have passed the House of Representatives and the Senate, shall, before it become a Law, be presented to the President of the United States; If he approve he shall sign it, but if not he shall return it, with his Objections to that House in which it shall have originated, who shall enter the Objections at large on their Journal, and proceed to reconsider it. If after such Reconsideration two thirds of that House shall agree to pass the Bill, it shall be sent, together with the Objections, to the other House, by which it shall likewise be reconsidered, and if approved by two thirds of that House, it shall become a Law. But in all such Cases the Votes of both Houses shall be determined by Yeas and Nays, and the Names of the Persons voting for and against the Bill shall be entered on the Journal of each House respectively. If any Bill shall not be returned by the President within ten Days (Sundays excepted) after it shall have been presented to him, the Same shall be a Law, in like Manner as if he had signed it, unless the Congress by their Adjournment prevent its Return, in which Case it shall not be a Law. Every Order, Resolution, or Vote to which the Concurrence of the Senate and House of Representatives may be necessary (except on a question of Adjournment) shall be presented to the President of the United States; and before the Same shall take Effect, shall be approved by him, or being disapproved by him, shall be repassed by two thirds of the Senate and House of Representatives, according to the Rules and Limitations prescribed in the Case of a Bill.

Section 7 speaks to the general passing of laws. Here, all government spending bills must originate in the House of Representatives, but also approved by the Senate, who may also propose amendments to those bills.

The remainder of this section deals with the process by which all bills may become law. First, a bill must be passed by both the House of Representatives and the Senate. Once this happens, the bill is sent to the President for his signature. If the President signs the bill, it becomes law. If he chooses to veto the bill, he sends it back to the Congress with his objections. If two-thirds of each house passes the bill again, it becomes law over the President's veto - an override. The bill also becomes a law without the President's signature if he doesn't sign it or veto it within 10 days as long as Congress is in session. If Congress is not in session and the President does not sign the bill, then it is as if he vetoed the bill and it does not become law.

The last section clarifies that this is the protocol for all bills to become law.

Up next week - three important sections that outline the powers of Congress and the limits on those powers as well as powers prohibited of the states.

Haiti

I wrote this poem 2 years ago after seeing a 60 Minutes story about the bodies just lying in the streets. May God bless Haiti.

Haiti

There is no dignity
when you die
poor, ten-thousand
at a time.
Your long dead
bodies lie in the streets
piled a dozen high,
some covered, most bare
to survivors stumbling
trance-like looking
for something resembling
normal. Not normal,
bodies in the streets rotting,
eyes open, staring but not
seeing survivors not
seeing a woman, a child
a mother, a daughter,
human beings
scooped together in death
dumped in a truck,
carted out of the city,
dumped in a hole in the ground,
thousands at a time,
alone -
no mourners, no music
no blessing of the souls.
There is no dignity
when you die
poor, ten-thousand
at a time.

(c) 2010 Jeffrey Seale

The Constitution - Article 1, sec 4-6

Much of the information in this series is found at The United States Constitution Online. I highly recommend this site for further exploration of the meaning of our Constitution and give it up front credit for many of the ideas written here.

Section 4 The Times, Places and Manner of holding Elections for Senators and Representatives, shall be prescribed in each State by the Legislature thereof; but the Congress may at any time by Law make or alter such Regulations, except as to the Place of Choosing Senators. The Congress shall assemble at least once in every Year, and such Meeting shall be on the first Monday in December, unless they shall by Law appoint a different Day.

This section outlines the process for electing the Congress and for their meeting. The power for setting elections was given to the states, but with a reservation that Congress could by law alter those regulations. It seems clear that the framers didn't necessarily intend for Congress to meet year round since the Constitution stipulated that they meet once each year on the first Monday of December. This part was later amended.

Section 5 Each House shall be the Judge of the Elections, Returns and Qualifications of its own Members, and a Majority of each shall constitute a Quorum to do Business; but a smaller number may adjourn from day to day, and may be authorized to compel the Attendance of absent Members, in such Manner, and under such Penalties as each House may provide. Each House may determine the Rules of its Proceedings, punish its Members for disorderly Behavior, and, with the Concurrence of two-thirds, expel a Member. Each House shall keep a Journal of its Proceedings, and from time to time publish the same, excepting such Parts as may in their Judgment require Secrecy; and the Yeas and Nays of the Members of either House on any question shall, at the Desire of one fifth of those Present, be entered on the Journal. Neither House, during the Session of Congress, shall, without the Consent of the other, adjourn for more than three days, nor to any other Place than that in which the two Houses shall be sitting.

Congress is given the authority to judge election disputes. It is also stipulated that a quorum must be present to carry out business. Congress is compelled to establish its rules of operation and discipline members as it sees fit. Further, the Constitution states that the proceedings of Congress be given in public record - clearly to promote transparency in government. However, it was recognized that some Congressional business must remain secret, i.e. national security issues.

Section 6 The Senators and Representatives shall receive a Compensation for their Services, to be ascertained by Law, and paid out of the Treasury of the United States. They shall in all Cases, except Treason, Felony and Breach of the Peace, be privileged from Arrest during their Attendance at the Session of their respective Houses, and in going to and returning from the same; and for any Speech or Debate in either House, they shall not be questioned in any other Place. No Senator or Representative shall, during the Time for which he was elected, be appointed to any civil Office under the Authority of the United States which shall have been created, or the Emoluments whereof shall have been increased during such time; and no Person holding any Office under the United States, shall be a Member of either House during his Continuance in Office.

Here, Congress is given the authority to set their own pay (this also was later amended). The next sentence gives them immunity from arrest in civil cases but not criminal cases. The protection of speech/debate clause was meant to protect the speech of Representatives/Senators from influence/intimidation from others, in this case particularly the other two branches of government. This turns out to be a rather important separation of powers clause.

The final clause stipulates that a member of Congress cannot simultaneously hold office in another branch of government.

 Next up: Article 1, sec 7

97

To say I don't remember a time when he wasn't around would be untrue. I remember the last 14 years easily. But I cannot recall a time as a child whenever he wasn't there.

He was the patriarch of the family. We all looked up to him. He was our rock. When I was about the size of that little fellow in the picture, he would let me sit on his foot and ride on his leg like a horse. I suspect that's about the earliest memory I have of PaPa. As I grew older, it was time for him to teach me about fishing, and fish we did. We would put our stuff in the back of his old pickup and drive to the lake. We made sure to get there just after sunrise because that was the best fishing time. We'd note who caught the first, the most, and the biggest. When I was 8, he gave me my first big boy fishing pole. Not long after, we went to break it in. I caught my biggest fish to date that day - a 3 pound bass. Of course, he had to help me land that bass, but it counted for me. I can't remember if it was the first nor if I caught any more that day, but it was definitely the biggest. We continued to fish together well into my teens.

He gave me my first job. As a young teen, I helped him cut the grass at the new retirement village. It was a rather large complex, and it took the two of us a day and a half to get it all done. Did I mention he was in his 60s and retired at the time? I got paid every week even though the complex was not always prompt about paying him. We eventually quit because they got so far behind in paying. When we weren't cutting the grass at the retirement home, we were probably out together cutting trees for firewood. Upon his retirement, he built a den on the back of the house complete with fireplace. That necessitated the procurement of wood to burn. And burn he did - 15 cords some winters. He instilled in us a steady work ethic. Hard work was a virtue.

College and grad school would find me and my cousin Alex spending the entire day Sunday sitting in his den watching football - from noon until 10 at night. We watched not only because he loved the Dallas Cowboys, but because we played fantasy football with each other and had to keep track of our teams. I think it's no coincidence that I lost my desire to watch pro football after his passing.



After graduation from grad school, I moved away from home. The distance necessitated at least a weekly phone call. He always asked about the weather and how work was going. I don't recall much of what we said, but I do remember he always had words of encouragement.

Today, he would have turned 97. A lot has happened in the 14 years since he died. Lots of great-grandchildren are now part of the family. He would have loved seeing them. All of the grandchildren have gone on to do really cool things. He'd be proud of each and every one of us. Not a day goes by that we don't miss him.

The Constitution Article 1, sec 1-3

Much of the information in this series is found at The United States Constitution Online. I highly recommend this site for further exploration of the meaning of our Constitution and give it up front credit for many of the ideas written here. Article 1 deals with the Legislative branch of our government - outlining the powers vested in the Congress.

Section 1 All legislative Powers herein granted shall be vested in a Congress of the United States, which shall consist of a Senate and House of Representatives.

The legislative branch was divided into two bodies with unique responsibilities. This further divided the power in government and assured difficulty in one party gaining too much power.

Section 2 Clause 1: The House of Representatives shall be composed of Members chosen every second Year by the People of the several States, and the Electors in each State shall have the Qualifications requisite for Electors of the most numerous Branch of the State Legislature.

This clause sets out the terms of electing the members of the House. Every two years, each member of the House must stand for election. The second part of that clause refers to the electors from each state. I believe this part is now outdated as we directly elect our members of Congress instead of voting for electors to represent our vote. The wording here is similar to the Electoral College used to formally elect the President.

Clause 2: No Person shall be a Representative who shall not have attained to the Age of twenty five Years, and been seven Years a Citizen of the United States, and who shall not, when elected, be an Inhabitant of that State in which he shall be chosen.

Here the qualifications to be a Representative are given - 25 years of age, a citizen for 7 years, and living in the state from which he has been elected.

Clause 3: Representatives and direct Taxes shall be apportioned among the several States which may be included within this Union, according to their respective Numbers, which shall be determined by adding to the whole Number of free Persons, including those bound to Service for a Term of Years, and excluding Indians not taxed, three fifths of all other Persons.2 The actual Enumeration shall be made within three Years after the first Meeting of the Congress of the United States, and within every subsequent Term of ten Years, in such Manner as they shall by Law direct. The Number of Representatives shall not exceed one for every thirty Thousand, but each State shall have at Least one Representative; and until such enumeration shall be made, the State of New Hampshire shall be entitled to chuse three, Massachusetts eight, Rhode-Island and Providence Plantations one, Connecticut five, New-York six, New Jersey four, Pennsylvania eight, Delaware one, Maryland six, Virginia ten, North Carolina five, South Carolina five, and Georgia three.

In this section, the number of Representatives from each state is given. Essentially, the number of Representatives from each state is determined by the population of that state. As you can see, the effects of slavery are in this clause as there is mention of "Number of free persons...". This section was later modified by amendment after the Civil War.

Clause 4: When vacancies happen in the Representation from any State, the Executive Authority thereof shall issue Writs of Election to fill such Vacancies.

Here, the power to fill vacancies in the House of Representatives is given to the executive of the state in which the vacancy occurs. This may be by appointment until such time as an election can be held.

Clause 5: The House of Representatives shall chuse their Speaker and other Officers; and shall have the sole Power of Impeachment.

The power of impeaching certain federal officers is specifically given to the House of Representatives.

Section 3 Clause 1: The Senate of the United States shall be composed of two Senators from each State, chosen by the Legislature thereof,3 for six Years; and each Senator shall have one Vote.

The makeup of the second legislative body is given here - 2 Senators from each state. In the House, representation is not equal. The number of Representatives is related to the population of the states. Here, the drafters of the Constitution leveled the representation by giving each state the same number of Senators. This gives equal footing to the less populous states.

Clause 2: Immediately after they shall be assembled in Consequence of the first Election, they shall be divided as equally as may be into three Classes. The Seats of the Senators of the first Class shall be vacated at the Expiration of the second Year, of the second Class at the Expiration of the fourth Year, and of the third Class at the Expiration of the sixth Year, so that one third may be chosen every second Year; and if Vacancies happen by Resignation, or otherwise, during the Recess of the Legislature of any State, the Executive thereof may make temporary Appointments until the next Meeting of the Legislature, which shall then fill such Vacancies.4

Again, the election of Senators is different than that of Representatives. Only 1/3 of the Senate stands for election every 2 years. Again, this helps equalize the power of the less populous states by keeping their Senators for a longer period. Also, this clause outlines the process for filling any vacancies.

Clause 3: No Person shall be a Senator who shall not have attained to the Age of thirty Years, and been nine Years a Citizen of the United States, and who shall not, when elected, be an Inhabitant of that State for which he shall be chosen.

Here the qualifications for Senator are given - 30 years old, a citizen of the US for 9 years, and living in the state from which he is elected.

Clause 4: The Vice President of the United States shall be President of the Senate, but shall have no Vote, unless they be equally divided. Clause 5: The Senate shall chuse their other Officers, and also a President pro tempore, in the Absence of the Vice President, or when he shall exercise the Office of President of the United States.

These clauses outline the leadership structure of the Senate. The Vice-President presides over the Senate, but only votes in the case of a tie.

Clause 6: The Senate shall have the sole Power to try all Impeachments. When sitting for that Purpose, they shall be on Oath or Affirmation. When the President of the United States is tried, the Chief Justice shall preside: And no Person shall be convicted without the Concurrence of two thirds of the Members present. Clause 7: Judgment in Cases of Impeachment shall not extend further than to removal from Office, and disqualification to hold and enjoy any Office of honor, Trust or Profit under the United States: but the Party convicted shall nevertheless be liable and subject to Indictment, Trial, Judgment and Punishment, according to Law.

These final 2 clauses define the role of the Senate in cases of impeachment. While the House impeaches federal officers, the Senate is given the power of trial. If the President is being tried, then the Chief Justice of the Supreme Court presides over the trial. In all other cases, the Vice-President presides (except, of course, in the case of his own impeachment). The maximum penalty for impeachment is removal from office, although the Constitution leaves open the possibility of further prosecution under the law.

Next up: Article 1, sections 4-6

The Constitution - a series, The Preamble

One of the the things I did over at LiveJournal after I made the switch was go through the entire Constitution examining its meaning in detail. I've decided to reproduce those entries here for the sake of posterity once LJ disappears into the endless loop of DNS attacks. I hope you enjoy!

Much of the information in this series is found at The United States Constitution Online. I highly recommend this site for further exploration of the meaning of our Constitution and give it up front credit for many of the ideas written here. The preamble is a declaration of why the Constitution was drafted. This is the part that we all memorize in elementary school, and for the Gen-Xers, learn through Schoolhouse Rock.

We the People of the United States, in Order to form a more perfect Union, establish Justice, insure domestic Tranquility, provide for the common defence, promote the general Welfare, and secure the Blessings of Liberty to ourselves and our Posterity, do ordain and establish this Constitution for the United States of America.

The first seven words are perhaps the most profound in all of the Constitution. From the outset, the powers granted to the government are derived from the People. We were established as a grassroots nation. The remaning enumerated reasons are rather self-explanatory. The first decade of our nation was governed by the Articles of Confederation and the founding fathers found them deficient in allowing for the governance of a new nation. And so the Constitution was written to better "establish justice, insure domestic tranquility, provide for the common defence, and secure the blessings of liberty..."

Finally, "to ourselves and our posterity" insures that the Constitution was meant to be a lasting basis for the government of the United States of America.

Up next week: Article 1, sections 1-3