Saturday, October 25, 2014

Regulatory Dynamism in Evolution

While the proteins stay mostly the same, the management evolves much faster.

When looking at evolution in the genetic code, we tend to focus on the most conserved elements which can take us the farthest back in time. Essential proteins like metabolic enzymes that we recognizably share with bacteria, or the translational apparatus of ribosomal RNA and related proteins, shared in all life forms. But to look at more rapid and recent evolutionary processes, one has to look at other parts of the genome which churn a lot faster and can be, incidentally, far more difficult to discern.

General illustration of regulation of gene transcription; DNA is the black/green line, the yellow lozenges are histones, and protein regulator binding sites are red. Various regulators bind near and far upstream of the gene, (whose start site of transcription is shown by the arrow, bottom right), all conspiring to promote or retard formation, placement, and activation of the initiation complex of proteins (blue) that includes the RNA polymerase.

The DNA sites that direct transcription tend to be such fast-changing genetic elements. They are short, often redundant, degenerate (able to accommodate various errors) and modular, meaning that they can occur in various positions and orientations with respect to their target gene and still work. Their shortness means that they can be born by mutational accident, and also that they are hard to recognize by text-comparison methods.

Human-mouse comparison of three protein regulators, (GATA, MAX, cMyc), and a brief stretch of DNA they bind to (red and blue). The blue MAX site in the middle was born in the primate lineage, while the others are recognizably conserved. From the top, the general coordinates of the genomic region, over this gene, EPB41, which encodes a protein that provides special flexibility to erythrocyte blood cells. Then various annotated features (colored bars) looking for regulator binding sites, then graphs of the physical binding data for each regulator (colored graphs).

They are also enormously important for evolution and biology in general. There are many hundreds of gene regulating proteins encoded by the genome, each of which bind to some DNA site, typically 6 to 16 base pairs long. These protein+site complexes constitute the first line of gene regulation, and, though virtually every possible aspect of biology can be bent to regulatory uses, typically the most sensitive and influential mechanism of gene regulation.
"... there are an estimated ~1700–1900 TFs [transcription factors, or regulators] in the human genome."
A recent paper discussed a new-ish method to study the phylogeny of such sites. The first step is to use a modern technology to find such sites, physically purifying such individual regulatory proteins while they are still bound to DNA in a cell, and later sequencing the underlying DNA snippets. This allows, for a single regulatory protein, all its target sites in a genome to be mapped (at least the sites being used under the condition used to grow the cells for the experiment, in this case erythroblast cell lines). The researchers did this (or actually got data from others) for several different transcriptional regulators in human and mouse cells.

 Then they used sequence comparison methods to deduce the history of these sites in the lengthy time of divergence between the two lineages, over the sequenced genomes of baboon, chimpanzee, rat, squirrel, tarsier, and other species. They used not only sequence conservation of the sites, but larger-scale studies of how the genomes relate to each other, called synteny analysis. This depends on large regions of diverged genomes being, at least on a patchwork basis, descended from each other, even if some of the sequences they contain are not so recognizable. Over time, various accidents in recombination and replication cause genomes to slowly re-arrange relative to their ancestors.

Synteny comparisons of human and chimpanzee (top) and human and mouse (bottom). The colors from one genome's chromosomes are projected / sprinkled as they correspond to the other genome. The Y chromosome tends to have a lot of junk or unrecognizable sequence.

The finding of this paper that is of general interest is: "Notably, between ~58–79% of all human TFBSs [transcription factor binding sites] had inferred origins after the human-mouse split." This is far more rapid change than one would see in encoded proteins, of which about 80% are recognizably shared between mice and humans. It follows that the regulation system, which controls where, when, and how much genes are expressed, is far more variable through evolution, than are the products of those genes. This makes sense when we see the slight variations over human populations and among closely related species that tend to concern relative sizes of bodies and parts, slightly more or less some some feature, coloration, etc. It fits very well with the typically gradualist nature of evolution, operating on thousands of genes and hundreds of thousands, if not millions, of their regulatory sites all in parallel over populations and time.

"For all six factors analyzed, the majority of human TFBSs [transcription factor bound sites] bound in vivo were originally absent in human-mouse common ancestor, which is consistent with previous cross-species comparisons noting substantial divergence in ChIP-seq protein-binding events across the two species and similar comparisons presented here, and is also comparable to detailed analyses conducted in Drosophila using alternative approaches" 
"Genes located nearest to hominid-specific binding sites were more frequently enriched for neural and sensory-related functions, and were in many cases involved in neurological pathways (Table S2). CTCF, MYC, and SOX2 target gene sets were all enriched for GO categories involved in sensory perception, while GATA1, MYC, ETS1, and MAX were enriched for neural development and differentiation categories."

  • Terrorists win ... in the US.
  • And in Afghanistan.
  • Annals of feudalism: the no-compete "agreement".
  • A jobs shortage, not a skills shortage.
  • The next financial crisis may come sooner than we think, at least to poor people.
  • In praise of helicopter money.
  • The shame of "rocket scientists" who work in finance / fraud.
  • This week in WSJ: "... the Obama economy ..." The definition of chutzpa and hypocrisy is to cause an economic catastrophe, then do everything in one's ability to stifle effective action against it, then blame the other party for the result.

Saturday, October 18, 2014

Thought Experiments in an Equal Pay World

Imagine ... what if everyone could get a job, and every job paid exactly the same? 

The labor market is highly problematic. It doesn't value people or work fairly, rewards destructive behavior (pollution, lawyering, lobbying, finance), and fails to reward socially constructive work (teaching, nursing, mothering, cleaning, farming). It tends to reinforce social hierarchies that have roots in patriarchy and class, perpetuating patterns that have questionable social value. Salary decisions are typically quite distant from business considerations, as CEOs have amply demonstrated, (both on their own behalf and over their minimum wage minions), depending more on the social and power relations of the parties involved.

There are also the persistent issues of gender and race inequality in hiring and pay- conditions that were supposed to have been solved by now, but which rear their heads again and again because of biases in the social system, if not in humanity itself. There is also the appallingly low pay provided by some of our biggest companies and industries (Walmart and farm labor come to mind) that rely on taxpayers to keep their shoddily paid employees fed, clothed, and housed. One way to solve all these problems would be to stipulate that all jobs pay the same wage. That average pay is currently about $44,322 per year, full time, in the US.

And if one is interested in addressing economic and social inequality in a comprehensive way, all the (progressive) solutions on the taxation side are trying to capture a horse after it has left the barn. The power that employers have now to pay rock-bottom wages to workers while paying themselves like kings means that they will likely have the means to make up for any tax increases. One solution is to insure that the labor market favors workers consistently, making jobs available to all, and using plenty of fiscal spending in times of slack private investment. But that simply works within the system, a system that is run, via our political and financial elites, by the incumbent powers of class and wealth, from which labor friendly policy is as likely to come as pennies from heaven.

Let's start with some easy issues first. How would currently high-paying professions be staffed if they were not paid differentially? Such work as financial engineering, dentistry, or medicine. Or CEO, lobbyist, sports star, political consultant, movie actor? The current system is, frankly, obscene in this regard. Would NBA teams not be able to field players if they did not paid them like kings? Probably, and one might get players who actually want to play, and they would be selected just as stringently, because the ancillary benefits of fame, status, and pleasure would remain, and the limited number of teams (and audiences) would remain likewise. More obscure fields like oil drilling, sales and marketing, dental hygienist, etc. might be more difficult to fill. But are they really paid that well? Typically not. It would probably just take some modest interest and training to attract people who otherwise might end up as farm workers or janitors, with less pleasant work conditions.

Similarly, the challenge and personal rewards of professions like medicine would remain and attract perhaps an even better class of trainees than they do now. Professions such as finance whose mind-numbing and pointless nature is now relieved only by their high pay might indeed contract, and frankly that would be a very good thing. So we would enter a world where students study what they are interested in, and enter professions that suit them, which select them on every basis of training and qualification as now, but without the lure of unusual monetary reward or penalty.

How about the low-wage work on which so much of the economy depends? Firstly, easily half of this work is completely useless. Unlivable wages allow many employers to hire far more people than needed, (fast food, retail; imagine being a walmart greeter), flood markets with low-margin franchises, and avoid efficiencies and mechanization. Labor shortages commonly spur efficiency gains. Secondly, a great deal of effort otherwise spent fighting against and dealing with unions might be saved by an equal pay regime. But in the end, paying people decently should come ahead of the consumer's ability to command the cheapest goods and services.

Entrepreneurialism is a somewhat more ticklish problem. How should we encourage business formation, innovation, family businesses, investment, and all the other energies of the free enterprise system if greed is no longer the central motivator? I think a general answer to that is to separate corporate and personal income on a stringent basis. If one wants to start a company that does great things, fine. One can grow it to globe-straddling size, but one can not pay oneself more than any other employee. That goes for bonuses, shares, etc.. all the remuneration that is now fair game would be strictly controlled, via the tax reporting system, and perhaps other enforcement, to one simple salary.

This relates to the problem of how investment would take place. Personal savings from such a system would probably be modest, and insufficient for the capital needs of the economy. People would generally be more dependent on (and willing to pay for) government programs to manage life-cycle savings, catastrophic contingencies, education, etc. I think one way to deal with the investment issue would be to allow special corporations (one might even call them "banks"!) and corporate entities like non-profits and educational institutions to have investment holding roles. Thus there would be a large ecosystem of investors and investments that do not significantly touch /affect personal income, but run large-scale investments in private enterprises due to the good judgement and personal values of the people involved. If the managers were unsuccessful, they might be demoted from their C-suites to street sweeping, but their personal income & sustenance would not be affected. One's social standing (and values) would be a much stronger aspect of motivation than greed, as would the personal satisfactions of the work one does. This would perhaps hearken back to the conditions in Antiquity, (occasionally, at least), when leading people and families competed to contribute to the state, not to leach from it, due to an intense sense of honor and reputation.

How about parenting? A fair system would pay for child care, whether done by parents or outside caregivers. So perhaps a parent could be paid through the first five years of a child's life if the parent decided to stay home, ideally at a full salary. This would make the decision to work or stay home shaped by personal preferences, such as career goals, rather than about finances. The same would go for care-giving to elderly parents and relatives, subject to some kind of certification that it is a full time occupation.

Perhaps the most difficult aspect of such a system is the impetus towards a black market, to under-the-table payments, gold-plated executive suites that pay in helicopter rides, escort services, etc. In our political system, with all the principles and deterrents against corruption, corruption remains rampant, indeed functionally legalized. Similar pressures would be inevitable in a tightly controlled equal pay system. Communist systems routinely elevated powerful people into great effective wealth, whatever their nominal salary. The best I could propose is again a strict separation between corporate and personal books, with transparency and strict regulation of what goes where. The current system of business tax deductibility, for example, requires extensive itemization and reporting, all to create an appalling drain on the public coffers, for the benefit of those need no such benefit. In the end, we organize society to limit some freedoms, (killing, fraud, theft), so that other and better freedoms may flourish. And perhaps the freedom to pauperize / feudalize your fellow citizens might not be as valuable as the freedom to have a decent and equitable life.

And how would this universal pay be set? It would be a broad economic policy exercise that fits closely with MMT (macro)economics. The tuning could be quite simple- if inflation threatened, pay would not be raised, while recession or deflation would be easily solved by raising the standard salary. Ultimately, its level and its value would be set by overall GDP and productivity, but the government, as the creator (and destroyer) of the currency, could easily make more or less of it and spend it in the form of salaries or other projects to fine-tune through any economic variation. Variations that, naturally, would be rare if not unheard of in this proposed society.

It is a thought experiment to imagine a system less besotted by greed, class, and injustice, more valuing of human e-qualities. One has to doubt its feasibility, but I believe it is a relevant ideal, or perhaps counter-ideal, for our time.

  • Worship of money and those with it, cont.
  • The middle class is kaput.. how did this happen in a democracy?
  • Gates on Piketty. 
  • "One side insists that the only important question is whether the truth-claims of religion are actually true; the other side says that question doesn’t even matter, and then wonders what “truth” is, anyway. It’s the overly literal-minded versus the hopelessly vague."
  • More on austerity.
  • Could we bring extinct animals back? But without habitat or stable climate, what would be the point?
  • Reality, as usual, has a liberal bias.
  • Meltdown in Iraq- the final chapter of Bushistic incompetence.
  • Bolivia- a happy case study of good governance and fiscal policy ... and throwing out the IMF.
  • On the impunity of finance.
  • Annals of feudalism ... Conoco bullies its employees.
  • The US deficit is low ... too low, as deflationary concerns drive the markets, and especially the specter of Europe melting down.
  • Sleep is really, really good for your brain.
  • Death might not quite as bad as imagined, either.
  • Insanity and religion ... not always either / or.
  • ISIS propaganda image of the week. Move along ... nothing Freudian here.

Saturday, October 11, 2014

Organizer Without a Brain: the Centrosome

The microtubule organizing center of eukaryotic cells, which guides mitosis and nucleates cilia.

One of the more immediate wonders of biology is the division of cells and the organized march of chromsomes that accompanies it, girdled by a beautiful web of microtubules. These microtubules all emanate from something called the microtubule organizing center (MTOC), or centrosome, which is itself strictly duplicated during cell division. It all looks so alive. Yet the process is one of molecules each doing their little thing in blind fashion to make a greater and very dynamic whole.

In this image of a large eukaryotic cell, DNA is stained blue, microtubules are stained green, and the centrosome is stained red / orange. At some point during the mitotic process, the kinetochores (possibly the pink/lavender spots) would line up strictly along the midline between the two centrosomes.

Centrosomes are special to eukaryotes- there is no trace of them in bacteria. They also have no DNA or other sign of being descended from some symbiotic or other bacterial forebear, unlike the mitochondrion or chloroplast, perhaps even the peroxisome. (Though some researchers find they contain a few special RNAs and argue for an endosymbiotic origin on that basis.) Yet they are quite complex organelles, based on the same tubulin that composes the microtubules of the cell generally, but with hundreds of other proteins added in. They organize not only the microtubule asters that drive mitosis, but also form the basal bodies of cilia- the flaggella of eukaryotic cells, again composed of microtubules. These cilia in turn have important, though only recently-discovered roles in mechanisensory and chemical signaling.

The centrosome and its component centrioles. The micrograph cross section shows parts of each centriole from one centrosome.

The centrosome is composed of two centrioles, one of which is the mother, and the other the daugher. At each cell cycle, they split apart and each grows another daughter centriole to reconstitute a full centrosome. Each centriole resembles a microtubule, which is a tube of nine paired tubulin tubules, but has an extra set of tubules, so nine triple tubules of tubulin. At the base of each centriole is something called a "cartwheel", which is made up mostly of a non-tubulin protein (Sas6) that forms a nine-fold symmetric ring that nucleates growth of the centriole, which in turn nucleates growth of the microtubule.

Detailed structure of microtubules (top) and the centriole (bottom). Note the two pairs of tubules in the microtubule, but triplets in the centriole, or basal body. The third tubule appears to template or make space for the dynein arms, which are the motors that allow cilia, for instance, to wave and move.

Models of the molecular structure of the "Cartwheel" protein complex, which  (d) templates and nucleates the centriole structure. Microtubules (purple) fit to the outside spokes of the cartwheel (blue). In the electron micrograph (e), three cartwheel stacks can be seen at the bottom, at the base of the centriole, and higher up, with lower electron density, the microtubule.

"Studies using human cells have revealed a mechanism that regulates cartwheel assembly through controlling the amount of SAS-6 in the cell. SAS-6 starts to accumulate at the end of the G1 phase and decreases in anaphase through proteasomal degradation mediated by APC/CCdh1 [19]. When the SAS-6 level is artificially increased by overexpression of non-degradable SAS-6, excess procentrioles are formed on the mother centriole."

Another electron micrograph of the centrosomes and their microtubule junctions.

The main component of all these structures is tubulin, the building block of all microtubules, which, along with actin, make up the cellular cytoskeleton of eukaryotes. Actin is smaller and free to form more flexible structures, (as well as being used to form the structural scaffold of muscle action), while microtubules make bigger structures (in cellular terms) like that which spans the whole cell for division, making cilia / flagella, and conducting cargoes along the enormous distances of nerve cell axons. Not all eukaryotes have centrosomes, (notably plants and yeast don't), but all have some form of microtubule nucleating center, (MTOC), of sometimes more modest construction. While microtubules are made of alpha and beta tubulin, the centrioles have a third form, gamma tubulin, which only exists at the nucleating base, not in the bulk structure.

Diagram of nucleation from a cartwheel (red) to a centriole (blue).

Unfortunately, less is known about how all this works dynamically than about its structural components. A recent paper covered two key proteins (Cnn and DSpd-2, in fruit flies) that seem to be all that are required to turn a bare centriole into a busy MTOC with hundreds of other proteins in a nimbus around it (the pericentriolar material). These key proteins are controlled by phosphorylation which is a common element of the cell cycle, and when turned on, come into the most interior precincts of the centrosome/centriole, and then migrate slowly outwards, with new molecules arriving at the center as long as the cell is in the requisite state.
"Mimicking phosphorylation allows the PReM domain [part of Cnn] to multimerize in vitro and Cnn to spontaneously assemble into cytosolic scaffolds in vivo that can organize MTs. Conversely, ablating phosphorylation does not interfere with Cnn recruitment to centrioles, but inhibits Cnn scaffold assembly. We speculate that, like Cnn, DSpd-2 can assemble into a scaffold and that this assembly is regulated in vivo so that it only occurs around mother centrioles."

At the other end, a good deal more is known about how microtubules attach to the kinetochores (structures at the center of chromosomes -at DNA centromeres- that anchor them to the mitotic spindle). This is not really in the scope of the post, but again, phosphorylation of key proteins is the theme, as is regulated assembly and disassembly of the microtubule itself. Disassembly right where it abuts the kinetochore causes shortening, thus tightening of the whole spindle, as long as the kinetochore has properly captured microtubules on/from both sides, i.e. both centrosomes, which is another complicated and phosphorylation-regulated process.

Example of a model for microtubule dynamics during one part of mitosis, with microtubules in purple,  (and unconnected microtubules in yellow, cell edge in gray), the centrosome in pink dots, and relevant motor proteins in green and salmon. The point is that, if relevant motors and attachment functions are regulated and happen at the right times, the system can accomplish complex tasks.

It is worthwhile to note that while the replication of the centrosome and its component centrioles is strictly regulated with the cell cycle, the same core system is used to create the basal bodies of cilia, and can create organizing centers from scratch. It does not require a pre-existing centrosome (unlike mitochondria, chloroplasts, and cells, which always come from pre-existing respective cells or cell-ish organelles). Sometimes, the basal body is the same as the centrosome; when cell division is done it migrates to the membrane. But many cells have multiple cilia, and each one has a newly created basal body at its base, whipped up without the complicated replication process. So it appears that replication is more a regulated restriction of MTOC creation than it is a necessary precondition of MTOC birth.

The science of the microtubule nucleation systems is still underway, but the direction is clear, as in any other area of molecular biology that has been laid bare to date. Molecules of some complexity, equipped with various means of regulation, such as regulated transcription and synthesis, outright destruction, interaction with various partners, or covalent modification like phosphorylation, neddylation, methylation, palmitoylation, GPI-anchoring, etc., can find their places and times of action in chemically explicable ways within a cell that is a vast, if microscopic, machine.

Saturday, October 4, 2014

Environmentalism is anti-American

Book Review of the biography of Rachel Carson, "On a farther shore".

Are we part of nature, or above it? Did god give it to us for our domination, or did we wriggle from its bosom to the condition of (bare) consciousness and power that threatens to undo the patient work of millions of years of evolution? Thousands of years ago, we had already killed off all our immediate ancestors in the hominid line and countless other species of megafauna. Now we have taken over most of the arable land of earth, comandeered much of the fresh water, polluted the rest of it, as well as the oceans, killed off many more species, doubled the concentration of CO2 in the atmosphere and the fixed nitrogen in the biosphere, and are facing ocean acidification and dramatic climate heating as an irreversible future fate.

But two generations ago humanity (and that would be the US) created the most immediately alarming and noxious dangers of all- nuclear weapons with their attendent radioactivity, and a fusilade of biocides and other poisons emerging from the postwar chemical industry- pesticides, herbicides, plastics, drugs, "food" additives, cleaners, etc. After a cavalier start to the era, when Las Vegas visitors turned out with their sunglasses to watch nuclear tests, the far-reaching dangers came increasingly to public consciousness, resulting in the above-ground nuclear test ban treaty of 1963, and the establishment of the EPA in 1970 and banning of DDT in 1972.

The reduction of nuclear radiation has been enormously successful, with negligible impact from current uses. The Chernobyl and Fukushima nuclear disasters have been the sole, and very large, blots on a very good record of radiation control (negligible amounts were released in the Three Mile Island disaster). Whether we want to use more nuclear power or not for the sake of climate change is a reasonable question.

Our record on control of biocides and other environmentally harmful chemicals, on the other hand, is far less impressive. Their use is less individually dramatic than that of nuclear technology, but their scale is mind-boggling. Every home and garden center hosts a biocide department that reeks to high heaven. DDT may have been banned, but an endless supply of other biocides have been concocted that are applied over the best land to kill all insects on it. The holocaust is ongoing.
"In 2006 and 2007, the world used approximately 5.2 billion pounds of pesticides"

Rachel Carson played a large role in our budding environmental awareness, both in her early work in books like "The Sea Around Us" that celebrated the beauty and interest of the natural environment, and in her last prophetic work on the dangers of the new pesticides, "Silent Spring". This biography is a worthy testament to her drive and talent which formed out of very unlikely materials (being a self-made professional woman in the 1950's) an earth-shaking message.

Indeed she could even be regarded as a significant religious leader, inspiring love for the world, and issuing prophetic warnings about its mistreatment at the hands of humanity, due in part to a lack of spiritual awareness, or misdirection. Humans have an innate religious sensibility about nature, and all the old religions treat it with reverence. The Celts had their sacred groves, worship of trees, and custom of bringing holly and mistletoe to their dwellings at the winter solstice. Unfortunately, the monotheisms, with their worship of a blown-up self-image, put nature into the shade as something to be dominated, something lost anyhow (Eden), even dirty and unclean. The unholy mix with post-war technologies allowed the dream to become a reality ... to "purify" the world of insects, vermin, disease, and all kinds of uncleanliness.

Obviously there is a great deal of good in cleanliness. But we learn that even our own health benefits from some amount of infection and dirt, lest our immune system idly turn its attention on our own tissues by mistake. Which is not to mention the wider ecological benefits of moderation and species diversity, and particularly in less wanton destruction of insects and other unheralded organisms that may not be the "stars" of our nature shows.

While we have banned the most noxious chemicals, (thalidomide, DDT, aldrin, lead arsinate, etc.), our systems and policies are simply not up to the task of protecting ourselves or the environment in a more comprehensive way. They are not precautionary, but rather wait for some dramatic harm to come to light before starting studies and investigations that take forever. The neonicotinoid insecticides are still being applied by the ton, despite their clear harm to bees (not to mention to all other insects).

Why? Principally, it is the agricultural and chemical interests, and their conservative allies, that fight chemical control policies every step of the way. There was once a time, when the EPA was founded, when conservatives were true to their name and cared about conservation, not only of their power, but of the environment as well. Those times are long gone, as the interests of the 1% diverge increasingly from those of the rest of society, indeed of humanity in general. Their loud patriotism tells us that government is bad, taxes always too high, scientists are all lying, and corporations always tell the truth. The worship of self has turned from a projected image of god to the even worse god of Mammon.
"It had only taken a few short centuries to move from a time when we gazed out at the ocean and wondered what was over the horizon. Now, she said, "our whole earth has become only another shore from which we look out across the dark ocean of space, uncertain what we shall find when we sail out among the stars." Based on the experience of her own generation- which had brought the world to such a dangerous crossroads- Carson said it was now time for the inheritors of earth and it many difficulties to finally prove human mastery not of nature, but of itself. "Your generation," she said, "must come to terms with the environment."

  • Wildlife is in dramatic decline.
  • Bees are in especially dramatic decline ... collapse.
  • Fly less to fight climate change.
  • On the psychology of evil, corruption, ideology, contradiction, hypocrisy, and other forms of humanity.
  • In the new economy, nice guys finish last.
  • Cute kids ... these days.
  • The recent US military campaign has little immediate effect. ISIS keeps gaining ground, and "One estimate puts the number of overall desertions for the Iraqi Army at over 90,000."
  • How and why the Fed shores up the global dollar system.
  • But banks run the Fed, so of course ... the Fed serves Goldman.
  • Goldman, Lehman, Enron.
  • AIG as a money-laundering bailout. "Alternatively, maybe Mr. Geithner simply felt that Goldman and the like had a more legitimate claim to billions of dollars in funds than the taxpayers who were footing the bill."
  • Bonanza gets one in against the bankers (Episode 284, The Trackers)
  • Pray our way, or the highway.
  • To screw workers, employers talk out of both sides of their mouths.
  • This week in the WSJ, annals of irony: "But does anybody in the government feel it is necessary to be truthful about anything anymore?"   
  • Economic graph of the week.. just how dramatically our economy has changed over the last 60 years. We've already had a class war, and we lost.