Freaky speaking- what we know about stuttering

Review of "Out with it", by Katherine Preston, with supplementary data.

Yes, I stutter. And it is a royal drag. Preston's book memoir about tells her story of the trials and travails of not being able to face the world with normal ease and confidence. Stuttering is specially odd because speech is such a rich medium, conveying emotion and status and so much else along with the explicit information. All that gets garbled up if one is fighting to get every other syllable out.

The first half of Preston's book is outstanding, portraying her trials in very affecting and articulate terms. The second half is where I (and she, until she drastically rewrote the project), was expecting to learn the most up-to-date science about stuttering, and branch out to the stories of other people. But unfortunately, it kept being about her, bringing the reader pretty much up to the very moment of Preston's life in the midst of manuscript writing.

Anyhow, let me fill in here with some of what the book should have conveyed. Stuttering is, as Preston relates, a maddeningly protean condition, coming in a wide spectrum of forms and severity. It is affected by emotional tenor, and remits after pretty much any novel therapy, but then returns again, afflicting the subject with guilt as well as disfluency. Is it caused by mean parents? Is it strictly a genetic and brain development condition? Well, some of each, but mostly the latter. Preston cites the most supportive and healthy parents possible, but one gets the sense that other cases get contributions at least in part from the family dynamic.

At base, stuttering won't happen without a biological predisposition, which is known to be highly heritable (as well as male-biased). 82% heritable in a recent twin study, in fact. Unlike other disorders whose genetics have been vague, full of false turns and bad statistics, a few genes have successfully been linked to stuttering, including GNPTAB, GNPTG, and NAGPA, which all function in a pathway important to lysosomes, the cell's recycling centers. They encode enzymes needed to tag the roughly 40-50 lysosomal enzymes, which collectively break down fats, proteins, and other molecules so that the cell can get rid of its waste. Lack of the tag leads to the enzymes end up mis-addressed, secreted outside, and thus to lysosomes that can't do their jobs. The stuttering mutations and their effects are only partial, though. Far more severe diseases are caused by more severe mutations- the type II mucolipidoses, which are fatal.

How all this leads to brain-specific issues, let alone speech-specific issues, is quite unkown. But the genetics is not going to lie, so there must be some mechanism by which, say, some neurons, at some stage of development, might be more sensitive to this internal deficiency than the rest of the cells of the body.. etc. etc. Perhaps enough lysosomal proteins leak out of the cell by the external secretion pathway (which is the default, when proteins are incorrectly targetted) that they mess up neuronal pathfinding or myelination during development. One can fill in the tech-talk ad libitum at the moment.

But these three genes only account for about 10% of the genetic ingredients of stuttering, so others, a few of which are known, may be more informative as to the mechanism. One is FOXP2, a transcription regulator which is known to be responsible for other, far more severe, speech deficits when more heavily damaged, and to be a target of evolutionary change in the recent human lineage, perhaps relating to speech acquisition among other things. Another is CNTNAP2, which operates just downstream of FOXP2 in the same pathway. But it has to be said that, in light of the general theory that stuttering is a developmental brain deficit, there is little liklihood that any of these genes / molecules will lead to some chemical cure. They had their effect back during development, and that cake is baked, so to speak. Incidentally, one paper maintains that "... a mouse model of stuttering may be possible.", which sort of boggles the mind!

Proceeding to the anatomical level, there has been quite a bit of brain scanning work on stutterers recently, with a wide range of targets and findings. The networks in play are speech recognition, in the auditory cortex, then Broca's area more related to speech production, and of course the general motor system, which comprises the cerebral motor cortex running over the midline of the brain surface from ear to ear, and its outputs through the spinal cord, plus important modulatory motor systems like the basal ganglia and the cerebellum.

Basic surface brain map, including auditory speech area (Wernicke's area) and the speech production area (Broca's area), which are heavily tied to each other, before leading to later motor areas in the motor cortex, cerebellum, brain stem, larynx, etc. Broca's area is heavily lateralized, being larger on the left than the right. Broca's area can also be referred to as Brodman area 44/45, the inferior frontal gyrus of the cortex, and as the pars triangularis / pars opicularis.

The most frequent finding is that the left side of the cortex, where Broca's area is notoriously lateralized, is short-changed a bit, and that the right side takes over somewhat more physical gray matter and speech functions. This leads to a hypothesis that reduced lateral dominance leads to a sort of speech train wreck, where both sides of the brain are trying to run one mouth, as it were, and not doing very good job of it.

Example of differential scanning of the brain's anatomy, in this case tensor imaging of white matter tracts connecting to or from Broca's area. The significant density difference indicates that the conduits between Broca's area and others are deficient in stutterers. Connection to the incoming auditory areas is particularly deficient.

But many studies have been done, finding variations in many of the various areas involved in speech, and disagreeing in certain respects. One gets the sense that the natural variability of people's brains, combined with the low numbers of subjects one can use for this kind of study, and perhaps the relatively small effects, makes it difficult to reach definite conclusions, though the field is still young. A brief bibliography:

• Evidence of Left Inferior Frontal–Premotor Structural and Functional Connectivity Deficits in Adults Who Stutter.
• Atypical brain torque in boys with developmental stuttering.
• Resting-state brain activity in adult males who stutter.
• Functional brain activation differences in stuttering identified with a rapid fMRI sequence.
• Motor excitability evaluation in developmental stuttering: a transcranial magnetic stimulation study.
• Brain activity in adults who stutter: Similarities across speaking tasks and correlations with stuttering frequency and speaking rate.
• Atypical caudate anatomy in children who stutter.
• Using Brain Imaging to Unravel the Mysteries of Stuttering.
• Corpus callosum differences associated with persistent stuttering in adults.
• Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation.
• Stuttering: a dynamic motor control disorder

On the bright side, treatment for Parkinson's disease in people who happened to also have stuttering, by the novel methods of deep brain stimulation in the thalamus has led to alleviation of stuttering, according to a couple of papers (though it also made it worse in others). What is the ventral intermediate nucleus of the thalamus? It seems to sit between cortical imputs and the cortical motor system, so it is involved in learning and regulation of motor behavior.

Given its negative effects, why is stuttering as prevalent as it is, for as long as it has been, from the earliest historical records? I think, like with many other conditions, it is a matter of balancing selection, whereby some of its genetic ingredients, when not all concentrated in a fully stuttering phenotype, correlate generally with high reactivity and fast reflexes. Which can have positive aspects, in a past world if not this one.

It is also worth noting how stuttering is one more example of the absence of a soul. Pending more thorough research, all signs point to it being a circuitry problem where developmental deficiencies cause some lack of coordination. No demon, soul, or higher power need be, or can be, invoked.

• Synanon and stuttering.
• Post-Christian, with a little nostalgia.
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• The IRS- another GOP whipping boy, starved to fail. Just like the post office.
• Public libraries totally rock!
• Gains slipping away in Afghanistan.
• Money, meaning, and happiness.
• Billionaires are not, typically, your friend. There is a class war, and they are winning.
• Social security, on the other hand, is, and helped enormously in the recession.
• Fracking for thee, but not for me.
• How do banks work? Still a matter of some controversy.
• What, exactly, is "public" about Facebook's corporate structure? Z-berg gets to spend the public's money.
• This week in the WSJ "A taxpayer needed a taxable income of $307,000 to enter the top 1%, a figure that hardly qualifies as "rich" today, especially in cities like New York, Chicago, Los Angeles or San Francisco."

A curious culture

The muslim encounter with the West; More from Bernard Lewis's "What went wrong?"

The last time I reviewed Bernard Lewis's book, "What went wrong? The clash between Islam and Modernity in the Middle East", I strongly supported an hypothesis he made in passing that Muslim women were perhaps the biggest problem of the contemporary Islamic world. That the patriarchial system of systematic disenfranchisement, sequestration, non-personhood, illiteracy, and non-education perpetuates not only a vast cultural deficit among women, but also among men, who are, after all, all raised by women.

Here I will take up a second thread from his book. That is the relative strength of the religious traditions within the Islamic and other cultures. Lewis lays out the unique strengths of Islam as follows:

"The children of Israel fled from bondage, and wandered for 40 years in the wilderness before they were permitted to enter the promised land. Their leader Moses had only a glimpse, and was not himself permitted to enter. Jesus was humiliated and crucified, and his followers suffered persecution and martyrdom for centuries, before they were finally able to win over the ruler, and to adapt the state, its language, and its institutions, to their purpose. Muhammad achieved victory and triumph in his own lifetime. He conquered his promised land, and created his own state, of which he himself was the supreme sovereign. As such, he promulgated laws, dispensed justice, levied taxes, raised armies, made war, and made peace. In a word, he ruled, and the story of his decisions and actions as ruler is sanctified in Muslim scripture and amplified in Muslim tradition."

The contrast with Christianity is particularly sharp. Christianity, as Nietzsche bitterly pointed out, is a loser religion. Jesus was tortured and killed by the Romans. He has never returned like he said he would. And if he ever does return, it will be hell on earth, as we are told in Revelation. Christianity had to be built on extreme cognitive dissonance, which had several effects. First was constant fission into sects and conflicting ideologies. If the core story is so unbelievable and requires such ideological gymnastics for palatability, it will naturally lead to conflicting interpretations and continuing dissatisfaction with any reigning interpretation. This was particularly evident in the early times of Christianity with the constant strife over the cannon, the creed, etc. And then it broke out all over again in the Reformation. There has been no reformation in Islam.

The second effect was a durable separation from the state. While medieval popes behaved more or less like full-fledged states, Christianity mostly fit the more traditional shamanistic role of advisor and arbiter of power, not the holder of power directly. Its internal doctrine was basically non-wordly, indeed highly impractical, and its model of Jesus was the epitome of the non-powerful, non-ruler. A giver of riddles and dreamy ideals more than than a tough Machiavellian. The Catholic church built this puzzle into an institution that invaded everyone's lives, took confessions, trafficked in the body and blood of its totem, made and unmade rulers, but never achieved what came naturally in the Islamic world- the full totalitarianism of the union of religious and temporal power.

As Lewis points out, the solution to the first problem in Christian Europe was the development of secularism and the civil society as a neutral zone among warring religions, giving up the totalitarian scope of most religions up until that point, in this case the ideological totalitarianism, if not the temporal. No such transition occured in Islam, which constitutes the manual of state, law, religion, morals, and a generally complete world view for its adherents. But this manual of state never underwent the kind of critique that happened during the enlightenment under Locke, Mill, Rousseau, et al. Or even underwent, as Europe did, centuries of gradual evolution of parliaments, the language of individual rights vs the state, and similar legal developments descended from Rome and in some instances from Christianity. So when the technology of modern state control entered the Islamic world, we ended up with lots of bad dictatorships, not democracies.

The excruciating developments in Egypt, where modern, democratic impulses have been smothered under the same old military model of strong-man government, dedicated to the proposition that the only loyal opposition is a dead opposition, goes to show how deep the cultural differences remain. The Egyptian government is hardly Islamic in any theocratic sense. It replaced an apparently more fundamentalist Islamic government. But contemporary fundamentalism is a false measure of authenticity, as it is merely a relatively modern reaction to the West and Westernization. The military dictatorship model is probably more traditional and durable in the Islamic world, going back to Muhammed himself, and certainly his successors. After all, that was the core of the Sunni-Shiah split: should the most powerful actor run the state and the religion, or should the most theologically / geneologically appropriate inheritor from Muhammad be given the keys? Sunnis have always chosen the former- a very practical choice, in a way.

But medieval stasis in political philosophy is hardly the worst of it. There is stasis in many other aspects of the culture, only glossed over by the fabulous wealth of the Muslim petro-states. There is a simple lack of interest in other cultures, in translations from other literatures, in science, in diplomacy, in art, in ideas that come from secular sources. While Europe's competitive ferment and legacy from Rome eventually generated endless inquisitiveness that is now institutionized in our universities, the grand Islamic schools of learning always "learn" about the same old thing ... the Koran. And not even using the critical tools that have blown up the study of ancient texts elsewhere.

• Gratitude, Afghan style. Just which side is the government on?
• Drug control can work, with public support and moderate policies.
• Affirmative action- coopting and false-carding the black middle class?
• Yes, an atheist world would be (will be) wonderful.
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• Yes, Dorothy, crime really is criminal. But does anyone have legal standing to fight it?
• Fossil fuel is so over.
• Or not .. without a high carbon tax, no other action will work. BP projects renewables at 7% of consumption in 2035. Is that acceptable?
• Social security needs to be increased. Because entitlements are ... good.
• In Europe, will festering economic failure turn into political disaster?
• Unearned money makes people conservative and mean.
• Martin Wolf for redistribution, and for robots.
• This week in the WSJ: "Reforming that public-school monopoly is the litmus test of seriousness on income inequality." It is truly incredible how WSJ columnists, who presumably are the intelligent creators of wealth and public good, can be so self-centered and blind. But I guess wealth does that.
• Image of the week- religion in the US.

Being and B.S.

Review of Martin Heidegger's Being and Time.

Martin Heidegger was a philosopher of the interwar and post-world war 2 period, and one of the founders of the continental school of modern philosophy which has headed into deconstruction and postmodernism. He coined the term existentialism, and is thought by many a leading or even the leading philosopher of the 20th century. His personal fixation was the question of being, to which he devoted what is deemed his greatest work, or even "towering achievement": "Being and Time".

In the development of modern philosophy, Heidegger stands against positivism and the whole analytical school, so I thought it worthwhile to read up on his ouvre. Surely something is lost in translation, but one does what one can. I can do no better than provide a few quotes, from a translation by Joan Stambaugh, 1977.

At the outset, he tries to forestall doubters:

"It is said that 'Being' is the most universal and the emptiest concept. As such it resists every attempt at definition. Nor does this most universal and thus undefinable concept need any definition. Everybody uses it constantly and also already understands what he means by it. Thus what made ancient philosophizing uneasy and kept it so by virtue of its obscurity has become obvious, clear as day; and this to the point that whoever pursues it is accused of an error of method."

And in the same vein...

" 'Being' is the self-evident concept. 'Being' is used in all knowing and predicating, in every relation to being and every relation to one's self, and the expression is understandable 'without further ado'. Everybody understands 'The sky is blue,' 'I am happy,' and similar statements. But this average comprehensibility only demonstrates incomprehensibility. It shows that an enigma lies a priori in every relation and being toward beings as beings. The fact that we live already in an understanding of Being and that the meaning of Being is at the same time shrouded in darkness proves the fundamental necessity of recapitulating the question of the meaning of 'Being.'"

He then discusses the origins of a scientific field from a vague intution to a metaphysical speculation, till finally it becomes a well-defined discipline, with methods, laws, theories, etc. Or at least I imagine that is what he is driving at.

"Being is always the Being of a being. The totality of beings can, with respect to its various domains, become the field where definite areas of knowledge- for example, history, nature, space, life, human being, and so on- can in their turn become thematic objects of scientific investigations. Scientific research demarcates and first establishes these areas of knowledge in rough and ready fashion. The elaboration of the area in its fundamental structures is in a way already accomplished by prescientific experience and interpretation of the domain of Being to which the area of knowledge is itself confined. The resulting 'fundamental concepts' comprise the guidelines for the first disclosure of the area. Whether or not the importance of the research always lies in such establishment of concepts, it true progress comes about not so much in collecting results and storing them in 'handbooks' as in being forced to ask questions about the basic constitution of each area, those questions being chiefly a reaction to increasing knowledge in each area."

Now we get into some heavy weather...

"The ontic priority of the question of Being. 

Science in general can be defined as the totality of fundamentally coherent true propositions. This definition is not complete, nor does it get at the meaning of science. As ways in which man behaves, sciences have this beings (man's) kind of Being. We are defining this being terminologically as Dasein. Scientific research is neither the sole nor the primary kind of Being of this being that is possible. Moreover, Dasein itself is distinctly different from other beings. We must make this distinct difference visible in a preliminary way. Here the discussion must anticipate the subsequent analyses which only later will become really demonstrative. 

Dasein is a being that does not simply occur among other beings. Rather, it is ontically distinguished by the fact that in its Being this being is concerned about its very being. Thus it is constitutive of the Being of Dasein to have, in its very Being, a relation of Being to this Being. And this in turn means that Dasein understands itself in its Being in some way and with explicitness. It is proper to this being that it be disclosed to itself with and through its Being. Understanding of Being is itself a determination of Being of Dasein. The ontic distinction of Dasein lies in the fact that it is ontological."

He seems to be trying to establish a conscious and self-reflective being as a special case of the general case of "being". In German, "dasein" means being (sein) there (da), which does not seem to add very much ... it is "existence" in any case, here or there.

Anyhow, one can imagine pages and pages of this, leading nowhere, and get a thorough sense of this text. It shares with its descendent postmodernism (not to mention its cousin theology) a sort of linguistic propulsiveness (with plenty of italics) and conviction of purpose without actually saying anything. Whether one agrees that, as Heidegger says, "The concept of 'Being' is rather the most obscure of all", he makes whatever it is less clear rather than more. It is a flood of sophism and pomposity that has led generations of all-too-serious students to strain their eyes and waste their talents, while setting itself up as some kind of tribunal of the highest, metaphysical kind over other fields.

• Free markets for thee, but not for me.
• Financial criminals reward each other with pay raises. And sycophantic press. And the uniquely powerful incentives to loot your own bank.
• Workers of the world will not unite.
• Yet unemployment is the worst fate of all.
• NASA is a happy-talk disaster zone.
• Eric Snowden's background.. how he reacted to army atmosphere: "Few of his new army colleagues, he maintained, shared his sense of noble purpose, or his desire to help oppressed citizens throw off their chains. Instead, his superiors merely wanted to shoot people. Preferably Muslims. ‘Most of the people training us seemed pumped up about killing Arabs, not helping anyone,’ he says."
• PIMCO guru pushes MMT: deficits create money and credit, which we need to support growth. Don't pay attention to all the mistakes I made last year, though, and the year before that, and ...
• This week in the Wall $treet Journal: "But the lesson from Europe is that the environmentalists who have been relentlessly hawking renewables are the real deniers." This piece makes a valid point, despite its hypocritical evasion of the appalling conservative denial of climate heating generally ... which is that transitioning to renewable energy is costly and difficult. Which is why we need a big carbon tax sooner, not later.

Fins are not fingers

The evolution of arms and fingers from fish fins, a story of genetic redeployment.

There is still a great deal to learn about how our bodies and minds rise out of our genetic code. Despite a growing flood of genomic data- and we are right on the verge of the $1000 genome, meaning that everyone in the developed world will shortly have their genome sequenced as a matter of medical routine- a vast gulf remains between the concrete knowlege we now have about the two ends of the process: genotype and phenotype.

One of the great American scientists of the 20th century was Edward Lewis of Cal Tech, who studied the developmental genetics of fruit flies, focusing on mutations that affected their body plan. In one example, he developed mutants whose third thoracic segment, instead of growing tiny winglets called halteres, grew full wings, just like their second thoracic segment. They were a little like dragonflies. This led Lewis on a long path to characterize such "homeotic" mutations, (which transform body parts), and to a Nobel prize.

It is now known that the main gene Lewis studied, "Ultrabithorax" encodes a transcription regulator that sits in the middle of a large developmental network or cascade of transcription regulators. The process starts from the glimmerings of polarity determination in the mother's egg, and proceeds through successively finer divisions of space and identity within the growing embryo until we get to the ultimate effector genes that direct neuron production and migration, or muscle development, or one of a thousand other cell types that generate our tissues.

The genes that Lewis studied are collectively termed "hox" genes, short for homeobox, which itself is short for a DNA-binding motif that is found in all these genes whose mutations cause homeotic transformation, which has a characteristic DNA and protein sequence, only subtly altered in each one. They are all related because they are all evolutionary copies of a single ancestor.

These genes sit in the middle of the developmental cascade, and have themselves vast upstream regulatory regions, to gather regulatory information from earlier stages in the process. Segmentation has happened by the point they come into action, and the homeotic genes integrate the data about which segment their cell is in, and, if conditions are right, turn on expression of their encoded regulatory protein, thereby providing input to all the downstream genes that actually prompt the development of that segment's proper parts, be they wings, legs, antennae, arms, etc.

Hox genes occur in tandem clusters, and the clusters themselves have been duplicated during evolution. In the diagram above, (from wikipedia), sea urchins, at the top, have something like the original cluster of eleven hox genes, color coded by their position in the cluster, which also relates to the position along the body axis where they are expressed (at right). Fruit flies, at the bottom, lost a few copies, and gained a few others, but retain basically the same system. Fish and tetrapods, in the middle, duplicated the entire set, copying whole clusters to various chromosomes, and lost individual hox gene units along the way. This elaboration allowed more complicated body plans to develop, with the example of fingers being a new use of the hox code, added onto the basic body trunk segment-by-segment code. The head and brain are another place where the hox system has been re-used in tetrapods.

One confusing element of the field is that in tetrapods, the hox A and D clusters are partly redundant. Each can, on its own, direct formation of arm and fingers, and both need to be deleted to eliminate the arm. So the researchers in today's paper mix and match from both clusters to make their various points.

"During mammalian limb development, the activity of both HoxA and HoxD gene clusters is essential and the absence of these two loci leads to rudimentary and truncated appendages."

In the embryonic hand, expression of many Hox D genes, from d9 to d13, are required to specify tissues during development, as are a few of the Hox A genes. They have overlapping patterns rather than some neat, digital(!) code, this being messy biology, but through mutation and other studies, researchers have pieced together some information about which gene of the tandem arrays does what. The genes have some individual characteristics, but much of their regulation is collective, directed from enormous regions on both sides of the cluster, comprising over three million base pairs of DNA.

The Hox D locus, on human chromosome 2. It contains eight distinct hox genes, (numbered black boxes at bottom), flanked by enormous control regions on either side which drive expression of some cluster genes in the hand (blue) and some in the arm (red), responding to transcription regulators earlier in the cascade of developmental patterning and differentiation. What are those fancy-looking blue and red cubic designs? That reflects a separate study where the authors physically tested which DNA was close to which other DNA in embryonic cell chromosomes. And they found that the right and left regions form their own knotted-up domains each hooking up with the central hox D gene, but not touching anything on the opposite side.

A recent paper is one of a pair that find that two clusters, hox D and hox A, are both flanked by very large regulatory regions that in fish have only slight differentiation, one directing slightly more distal (towards the outside) expression than the other one (red). The large regulatory region downstream (red) which originally specified expression in fish fins, has pretty much retained the same function in tetrapods, specifying the arm.

But the large regulatory region on the other side (blue) in fish only adds a little bit of extra expression to some cluster members towards the outside of the limb. In tetrapods, however, it specialized to direct expression of hox D genes in the hand, quite exclusively from directing expression anywhere else. The basic finding is that fish fins are not proto-fingers, really, but are related principally to our arms. The fingers arose from a mostly new regulatory program established by the blue areas in the genome shown above. And the wrist ... that is specified in the gap, partly by the lack of hox expression. It is interesting to note as an aside that the hox B and hox C clusters seem to have regulatory control only from one side, not both sides.

Inference of the paper, that the hand-specifying regulatory  regions of hox D and hox A (blue) developed from earlier regions (yellow) that had relatively minor roles in fish, and which specified the margin of the fin, rather than a separate structure.

What is some of their evidence? Well, first, let's see some of the native expression of mouse hox A genes:

Expression of individual genes from the mouse hox A cluster, showing finger-specific expression for 9, 10, 11as, and 13. The exception of hox A11 is striking, as a departure from the hand-specific pattern of its nearby siblings, and in its well-defined zeugopod, or lower-arm expression pattern.

One obvious experiment was to transplant the fish hox DNA into mice to ask where it gets expressed. It always gets expressed in the same place- where the arm expression happens, at the base of the limb bud, not where finger expression happens. This makes the case pretty strongly that finger expression and development was, as one might imagine, a novel evolutionary development.

Mouse embryonic limb buds showing the expression of a transgenic zebrafish hox A cluster, with regulatory regions and genes it contains, including each of the ones as labeled. They all get expressed in the near, or arm region, not in the finger region. This was true no matter which regulatory region of the zebrafish hox A cluster was used, whether the upstream or the downstream side.

Even more striking, the researchers show expression patterns in complete embryos. Below is a stage E11.5 mouse embryo with transgenic fish hox A13, driven by the fish regulatory region corresponding to what would be the hand/finger-specifying region on tetrapods. Its expression appears in many areas of the body, but not in the fingers, as the mouse's own hox A13 does. It is worth noting that in vertebrates, the hox genes are used all over again in specifying brain region development, which does not happen in flies. It is a common theme- that through the accumulation of regulatory complexity, the same genes can be re-used many times to create ever more elaborate phenotypes.

As you can see from the genome locus diagram a few figures above, the regulatory regions controlling the hox D genes are far, far larger than the protein-coding genes themselves. Complexity of control is the theme in all genomes, especially ours. These regions contain many little modular bits of DNA that bind to various other transcriptional regulators that operate from upstream in the developmental cascade, allowing a progressive, step-by-step, though in actuality a stochastic and mix-and-match evolutionary process whereby the silk purse of our present bodies are made out of the sows' ear of a few thousand ancient genes.

• 23 & me genetic testing- another front in privacy and big data.
• Example of another paper on limb formation, in the transcription regulator cascade of development.
• Creationism map.
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• The patent backstory to the Google, Motorola, and Nortel deals.
• Fascism, American style- corporations and the blacklist.
• Economic quote of the week, from John Schmitt:

"Workers today are a lot older than they were in the 1960s or the 1970s, and they are enormously better-educated than they were in the 1960s or 1970s. The fact that most workers are doing barely better, and some workers are doing worse than their counterparts from 40 or 50 years ago … suggest that the problem is that the way the economy converts people’s skills, people’s experience, people’s education and their training, into good jobs is what has deteriorated over this period. Not people’s underlying skills, or work experience, or education."