Thursday, November 20, 2014

Lighting the Cambrian Fuse

A trilobite from the Burgess Shale fossil beds of British Columbia. Photo: Mary Caperton Morton

Burgess Shale Fauna, 1989, Carel Brest van Kempen

Half a billion years ago, dramatic changes swept across the planet. In an evolutionary surge, the ancestor of virtually every living animal group emerged. It was the most extraordinary evolutionary event since life had first begun; in a flurry of diversification, complex multicellular life burst into existence, ending the 3-billion-year reign of bacteria and archaea as Earth's dominant life forms.

Fossil records show that during a comparatively short time, every major basal body plan appeared, including arthropods, mollusks and chordates, the lineage which eventually led to humans.

No one knows what triggered this remarkable event, but in 2013, researchers began to fit major pieces of the puzzle together for the first time. We now know that 600 million years ago, violent tectonic upheavals thrust mineral-rich rocks up from deep within the Earth's mantle, forming a colossal mountain range some 2,500 kilometers long across the supercontinent Gondwana, over most of what was to become west Africa and northeast Brazil.

Just like today's Himalayas, this massive pre-Cambrian mountain range was subject to constant, intense erosion, which fed Earth's ancient oceans with tremendous rivers of mineral sediments, radically altering oceanic chemistry.

This was during the Edicarian period, in which the genetic toolkit - body-patterning genes necessary for the eventual emergence of complex animals - seems to have first evolved, some 60 million years prior to the Cambrian. These genes were the legacy of rather... odd... life forms, mysterious creatures which vanished from the planet at the close of the Edicarian, well before the Cambrian began.

Thus, the creatures of the Cambrian did not suddenly appear from nowhere, contrary to the ill-informed claims of religious fundamentalists; there had been tens of millions of years of evolution before the Cambrian. So while it has been cast as a mysterious "explosion" of life, the Cambrian radiation it isn't out of line with simple evolutionary principles. It's also important to remember that "sudden" is an extremely relative term: when one is referring to deep time - epochs of hundreds of millions to billions of years - 20 million years may be comparatively short; but that is still at least one hundred times as long as humans have existed in their present form.

But immediately prior to the Cambrian explosion, there's a prominent, planet-wide gap of "missing time" in the rock record, referred to as the Great Unconformity. Here, a prominent rock boundary separates ancient igneous (volcanic) and metamorphic (altered by heat and pressure) rocks from significantly younger sedimentary ones - those formed by settling materials.

It was long believed that the Great Unconformity was just a gap in the evolutionary record, before multicellular life evolved with shells or bones capable of hardening into fossils, but now researchers say the period's chemical influence upon Earth's ancient oceans promoted biological calcification - the development of the first shelled and bony animals. Thus, the processes which led to that gap may actually have triggered biomineralization, lending impetus to the Cambrian period's evolutionary explosion.

We know for certain that, during the Cambrian, the rapid increase in animal diversity included a global increase in biomineralization, as animals began to evolve hard shells and skeletons. This not only allowed early animals to become preserved as rock fossils, but, coupled with the emergence of Earth's first carnivores, these hard structures seem to have helped trigger an "evolutionary arms race" between predators and prey, resulting in the Cambrian radiation.

Geological evidence gathered from across five continents shows that by 540 million years ago, North America had ripped away in tectonic shifts, carving a deep oceanic gateway between the ancestral Pacific and Atlantic oceans, and isolating Laurentia - North America's ancient core - from the supercontinent Gondwanaland. The event also caused a global rise in sea levels, spreading shallow ocean water across the planet. This redistributed deeply buried minerals, further altering Earth's ocean chemistry, and increasing available atmospheric oxygen - all conditions which helped foster the divergence of complex, multicellular life.

Continental weathering left a gap in the geological record all around the world as sea levels climbed, scrubbing the continents clean. The shoreline gradually crept to ever higher elevations, and wave-base razors washed away soil and sediment which had built up from the breakdown of ancient rock. This cleared away materials which would otherwise have settled into sedimentary rocks, exposed huge ranges of bare bedrock, and rapidly swept ionized minerals into the ancient seas.

Shallow inland seas helped promote continent-wide erosion, allowing fluctuating weather to break down rocks, while rivers carried the sediment out to sea. The geological record shows that, in the wake of a probable ice age, severe storms intensified this erosion of ancient, mineral-rich rocks: strontium-87 isotopes (atoms with more neutrons than normal), generated by the weathering of continental rocks, peaked during the pre-Cambrian, showing intense and lasting erosion had occurred. This drastically altered the composition of seawater, increasing its calcium and sodium ion concentrations.

Because excess calcium interferes with vital cellular signalling, it's thought that the first marine shells came from marine organisms excreting excess cellular calcium. But these shells offered a distinct evolutionary advantage, sheltering their hosts from predation.

According to Harvard University's Erik Sperling, hypoxia (low-oxygen states) had long held evolution in check, limiting the abundance and diversity of animals, particularly carnivores. But the increase in available oxygen at the start of the Cambrian allowed for a much more efficient processing of food - the carnivorous diet. Higher oxygen levels also allowed multicellular species and body structures to emerge and rapidly diversify for the first time.

The combination of factors triggered adaptive radiations - the rapid diversification of one lineage into several new ones, each with different adaptations to the environment. Such adaptive radiations are all responses to opportunities, as creatures evolve physical or behavioral traits which enable them to exploit newly-available niches or resources.

A single key adaptation has the potential to open up several new niches for an organism, and act as a catalyst for an adaptive radiation. One example is the gradual transformation of reptilian jaw bones into the ossicles - tiny, ultra-sensitive ear-bones which enable land animals to amplify fluctuating air pressure (sound waves). While inefficient within an aquatic environment, they provide an excellent means for creatures on land to locate prey - or escape hungry predators.

While some animals specialize to take advantage of specific food resources, new, unpopulated environmental niches or an escape from competition can also lead to adaptive radiations. Such a process allowed mammals to rise to dominance, when a meteorite the size of Mt. Everest slammed into the ancient Gulf of Mexico 66 million years ago, dooming the dinosaurs.

Sources: "Dawn of Carnivores Explains Animal Boom in Distant Past", press release, Mario Aguilera, July 30, 2013, University of California, San Diego
"Massive Geographic Change May Have Triggered Explosion of Animal Life", press release, Anton Caputo, November 3, 2014, University of Texas at Austin,  
"Missing Rocks May Explain Why Life Started Playing Shell Games", Scott K. Johnson, April 25, 2012, Nature 

Monday, November 10, 2014

All for One and One for All - How Multicellular Life Began

Petri dishes growing various strains of Pseudomonas fluorescens bacteria. Researchers were able to watch individual cells evolve into multicellular entities capable of self-reproduction. Photo: Gayle Ferguson, Max Planck Institute for Evolutionary Biology, Plön, Germany.
Genetics studies show that multicellular life evolved from single-celled creatures. This required formerly independent cells to cooperate - but what might have induced them to override self interest and cooperate in the first place?

By integrating bacteria into a special two-phase life cycle, international researchers observed and recorded individual cells evolving into self-reproducing, oxygen-acquiring tissue - one that engages in a division of labor, generating reproductive cells.

Such life cycles were originally "...a spectacular gift to evolution. A developmental program evolved which merged these cells into a single organism - benefiting groups, as formerly independent cells came to work for the good of the many", says Max Planck Institute's Dr. Paul Rainey.

Pseudomonas fluorescens bacteria usually live singly, but some mutations result in cells which excrete adhesive glycoproteins - gluelike carbohydrate-protein compounds. These cadherins can attach cells to one another after they have divided. The resulting cellular assemblies are better able to survive under certain environmental conditions, despite the biologically expensive cost to the individual cells excreting the cellular glue.

In this experiment, Pseudomonas fluorescens was cultured in unagitated petri dishes, where oxygen would be most abundant at the surface. Cell colonies were best able to benefit from this condition by forming mats which floated upon the liquid surface.

The logical problem with this adaptation is that natural selection should favor "cheater cells" - those which don't produce biologically expensive adherons, but instead exploit the already-existing mat surface to promote their own quick growth.

In biology, cheaters are individuals which take advantage of communal efforts without expending any efforts themselves. In this case, however, the success of cheater cells means the defeat of the population as a whole: an abundance of cells which don't produce adherons clinging to a mat will cause it to collapse and fall to the bottom of the solution, where the entire community then suffers from oxygen deprivation.

This means, says Dr. Rainey, "No sooner do the mats arise, than they fail: the same process that ensures their success - natural selection - ensures their demise."

To find a workaround, his team set up differing life cycles between two bacterial colonies. The first colony experienced a two-phase life cycle, with cheater cells functioning as germ line cells - specialized for reproduction. Such two-phase life cycles are similar to those among most modern multicellular organisms.

The second group was purged of cheater cells, and the mats grew through fragmentation.

Interestingly, both populations succeeded and increased when they were allowed to compete with one another in the same petri dishes.

What's more, cheaters in the two-phase populations grew to sacrifice their individual fitness in the interest of the whole, reproducing at a lower rate. This meant natural selection had begun favoring collective cells over individual ones, which had begun "working for the common good".

This means the two-phase population had evolved into a new multicellular entity whose hardiness was no longer due to the fitness of individual cells within the collective.

In addition to solving a long-standing evolutionary mystery, these experiments may eventually help reveal the origins of soma (diploid, standard cells) vs. germ (haploid, reproductive egg and sperm) cells, according to Dr. Rainey.

Pseudomonas fluorescens are a group of common, non-pathogenic (non-disease-causing) saprophytes (organisms like fungi which feed upon dead organic matter) which colonize soil, water and plant surfaces. The name "fluorescens" refers to the greenish glow the bacterium produces. It moves about by means of multiple whip-like "flagella" and subsists upon mineral salts and carbon.

Because many varieties of P. fluorescens protect plant seeds and roots against fungal infection,  it is being extensively investigated for agricultural uses. Experiments are also underway to exploit its ability to partially or completely degrade environmental pollutants such as styrene, TNT and PAHs (polycyclic aromatic hydrocarbons), fossil fuel pollutants known to be carcinogenic.

Sources: "From single cells to multicellular life: Researchers capture the emergence of multicellular life in real-time experiments, press release, Max-Planck-Gesellschaft, November 5, 2014.;

"Pseudomonas fluorescens", MicrobeWiki, 2014

Sunday, November 9, 2014

The Titanic Mountain Range that Jumpstarted the Cambrian Explosion

Professors Joerg Hermann and Daniela Rubatto examine the composition of rocks from a long-vanished massive mountain range over half a billion years old. Photo: Carlos Ganade de Araujo
Australian National University scientists have just filled in another piece of the puzzle that was the Cambrian Explosion - the rapid growth and diversification of multicellular life that began about 542 million years ago.

600 million years ago, a huge mountain range the scale of the modern Himalayas ran some 2,500 kilometers across the supercontinent Gondwana, spanning much of what would become west Africa and northeast Brazil.

According to Professor Daniela Rubatto, this mountain range was so massive, it was subject to constant, intense erosion, just as the Himalayas are today. That erosion fed mineral sediments into Earth's ancient oceans, providing a massive and constant flow of rich, life-sustaining nutrients that would feed an explosion of evolutionary development.

Scientists have long proposed that a massive mountain range provided the chemicals necessary to radically change ocean chemistry and feed an explosion of multicellular life, but Dr. Rubatto and his co-researcher, the University of Sao Paulo's Dr. Carlos Ganade de Araujo finally found the ancient remains in 2013.

These mountains, formed by a collision of continents, vanished long ago, worn down over half a billion years. At the time of their formation, the violence of the continental collision, forced rocks from the Earth's crust 100 kilometers into the mantle; there, enormous pressures and baking temperatures formed unique minerals that were vital to evolutionary processes in the Earth's pre-Cambrian oceans.

Professors Hermann and Rubatto explain their work here:

Source: "The Ancient Mountains that Fed Early Life", press release, Australian National University, October 16, 2014

Thursday, November 6, 2014

From Bugs to Brains

Top: The head of Panthropus boisei - "Nutcracker Man", as recreated by anthropological sculptor Elisabeth Daynès Bottom: The skull of Paranthropus boisei, Nairobi National Museum in August 2012. Photo: Bjørn Christian Tørrissen
The human brain is a biologically expensive luxury in terms of caloric needs, mainly because glucose is critical for powering protein ion pumps that maintain the resting membrane potential - the difference in charges between the inside and outside of neuron cells. It is this built-up charge that allows neurons to fire and send signals to other neurons "downstream" in the brain's circuits.

But the human brain's rather sudden and enormous growth in complexity and bulk is something of a mystery. What led to this incredibly rapid (in terms of geological time) evolution? Previous studies have shown that the dietary addition of DHA from aquatic animals was a major factor, providing new essential fatty acids that spurred rapid evolution of hominid brains.

Now studies at Washington University in St. Louis point to a much less palatable source of additional proteins which drove primate brain growth - insects.

In times of scarcity, our primate ancestors turned to insects to survive - and learning to harvest hard-to-reach bugs like ants and slugs helped spur brain expansion and higher-level cognitive abilities.

Anthropologists have long recognized that the challenges of surviving in a rapidly changing environment - i.e. finding food and shelter - were important for brain and cognitive development in primates, according to anthropology professor Dr. Amanda D. Melin (although it may also have been due to mere happenstance in the form of a minor gene-duplicating glitch).

Digging for insects during times of scarcity likely helped spur hominid cognitive development, and may have helped prepare our ancestors' brains for tool use and manufacture. A number of human communities worldwide have long consumed burrowing insects, further bolstering theories that this played a major part in the evolution of the human mind.

By observing the effects of seasonal food supply changes upon foraging patterns among wild Costa Rican capuchin monkeys over the course of five years, Dr. Melin and her team found direct evidence linking the mental challenges of foraging for insects and other difficult-to-obtain foods with problem solving, sensorimotor development and tool use.

Seasonally, when more appetizing fruit isn't as readily available, some primates intensify their feeding upon embedded insects. Thus insects constitute an important "fallback food". Such fallback foods contribute to both cognitive and "morphological" evolution - the gradual development of primate body forms, such as teeth, jaws, and specialized digestive systems.

The influence of insects and other fallback foods upon primate brain evolution is most pronounced among primates found in habitats that experience wide seasonal weather swings, like the wet/dry cycles of some South American forests. Obtaining insects burrowed in tree branches or under tree bark is cognitively demanding, but with a high nutritive payoff, in the form of calorie-dense fats and proteins, which fuel the development of big brains.

However, some varieties of capuchin monkeys are more adept at tool use than others. Dr. Melin's work provides a possible explanation. For example, there is a significant difference in tool use between Sapaju (robust tufted) vs. Cebus (gracile untufted) capuchin monkeys.

Cebus monkeys are clever at tricks for harvesting food - banging fruit and snails against branches, but their Sapaju cousins are much better at the inventive use and modification of comparatively sophisticated tools.

Mitochondrial DNA analysis indicates the Sapaju-Cebus split happened during the late Miocene period, millions of years ago.

Cebus capuchins have long occupied tropical rainforests, while their Sapaju cousins spread from their original Atlantic rainforest habitat to drier, more temperate and seasonal climes.

Natural selection of course favors primates who are healthier - thus better able to eat, in this case by developing advanced sensorimotor skills gained from extracting hard-to-get fallback foods. Thus some capuchin groups have evolved to be better at using tools.

Among our ancient hominid ancestors, Paranthropus boisei (Nutcracker Man)left behind fossilized teeth - careful chemical analysis has detected traces of several extractable foods, including termites, roots, grass bulbs and tubers.

To this day, in many human cultures around the world, insects become seasonally important sources of protein when other animal foods are scarce. Dr. Melin's study indicates that surviving on a diet of such creatures insects was key to the development of human skills, and that insects may well have played a major role in human brain evolution.

Source: "Seasonality, extractive foraging and the evolution of primate sensorimotor intelligence", Amanda D. Melina, Hilary C. Young, Krisztina N. Mosdossy, Linda M. Fedigan, Journal of Human Evolution, June 2014

Monday, November 3, 2014

Your Squirrely Cousins

A reconstruction of Jurassic forest mammals, depicting three new species of haramiyidans (from left Shenshou lui, Xianshou linglong, and Xianshou songae) as well as a gliding species and another previously-discovered haramiyidan (right). Illustration: Zhao Chuang

Fossils of Senshou lui (left), Xianshou linglong (Top right) and Xianshou songae (Bottom right). Photo: Jin Meng.
One of the oldest mammals yet discovered was an ancient squirrel-like creature named Shenshou lui, found in China's northeastern Liaoning province. Its name is derived from the Mandarin words for "heavenly animal" and Lu Jianhua, the man who discovered the specimen in 2013.

Shenshou's remains were found alongside fossils of two similar ancient tree dwellers, dubbed Xianshou songae ("celestial beast" found by Rufeng Song) and Xianshou linglong ("exquisite celestial beast"), in a layer of rock 160 million years old. Shenshou was the largest of the three species, weighing about ten ounces, and the size of a small squirrel, while the other species were the size of house mice.

All three are members of the haramiyid family, now shown to be among the first mammals. These three species thrived in what is now China during the Jurassic period, alongside jaw-droppingly huge titanosaurs such as the seven-story-tall titanosaurus.

The haramiyid fossils were unearthed by amateur paleontologists in a cornfield, in a region famous for its cornucopia of dinosaur fossils, all discovered within the last half-century. During the Triassic period in which the haramiyids first appeared, this region was blanketed by tropical forests which teemed with dinosaurs, mammals and pterosaurs, on the ancient supercontinent of Laurasia, which would eventually separate into the modern northern continents.

It was long believed that, rather than true mammals, the haramiyids were only protomammals from the Synapsid lineage. However, these newly-discovered specimens, including a complete skeleton, provided American Museum of Natural History paleontologist Dr. Jin Meng and colleagues with evidence that haramiyids were in fact true mammals. The newly-discovered fossils include a skull, teeth, and skeletons definitively showing that Shenshou and its haramiyid kin were basal mammals.
This discovery demonstrates that mammals evolved earlier than paleontologists had realized, pushing back the divergence of mammals from reptiles at least 25 to 50 million years; the earliest known member of the haramiyid group being between 220 million and 201 million years old.

Haramiyids lived an arboreal existence, scampering among the treetops, out of reach of larger predatory dinosaurs on the ground, as evidenced by their slim, light, and graceful bodies, their long, monkey-like prehensile tails, and their long fingers, which resemble those of more modern branch-grasping treetop-dwellers. They had teeth adapted to an omnivorous diet of fruit, nuts and insects. All three species also appear to have had ossicles - three uniquely mammalian middle ear bones, which amplify sound, providing excellent hearing in a terrestrial environment.

Because of its body features and large incisor teeth, Shenshou superficially resembles modern squirrels, though the species are not directly related. In fact, the haramiyids were quite different from any species alive today. Any similarities to be found between these ancient creatures and modern ones are the result of convergent evolution, the independent development of structures with similar form or function among creatures of very different ancestry, such as the independent evolution of wings among birds and bats.

Scientists have known about the haramiyids since Darwin, but only from fossilized teeth and fragmentary jaws. Because of this scarcity of well-preserved specimens, their status as mammals or mammal-like reptiles has long remained something of a mystery, according to Dr. Meng.

Living during the same period as the haramiyids were the small rodent-like, egg-laying members of the multituberculate family, a sister group whose Latin name refers to the complex cusps of their teeth. Multituberculates were long known to have been mammals, and were believed to have been the only major mammalian branch to have gone entirely extinct, leaving no surviving descendants. In their time, however, they were enormously successful, eventually spreading throughout the ancient world for over 100 million years, longer than any other mammal group.

Both the haramiyids and the multituberculates eventually died out however, leaving no living descendants, having long ago diverged from the lineage which would lead to Earth's modern mammals. They appear to have been outcompeted by early rodents, which first emerged some 34 million years ago, during the Oligocene period.

According to Dr. Meng, his team's findings mean we need to revise our picture of our prehistoric mammalian ancestors as "...shrew-like insectivores that lived in the shadow of the dinosaurs".

The earliest mammals evolved in many divergent directions from the outset - over the last half century, a number of fossil discoveries are showing that early mammals occupied a variety of ecological niches, swimming, walking on the ground, digging burrows, and gliding in forest canopies, he notes. Ancient mammals like the haramiyids and multituberculates were just as varied as modern-day rodents like beavers, gophers, mice, porcupines and squirrels.

Sources: Chisel-Toothed Beasts Push Back Origin of Mammals, Brian Switek, National Geographic, September 10, 2014;

Three Jurassic Squirrel Species Discovered in China, Sergio Prostak, Science News, Sep 11, 2014;

Three new Jurassic euharamiyidan species reinforce early divergence of mammals, Shundong Bi et al., Nature magazine, September 10, 2014;

Ancient Squirrel-Like Creatures Push Back Mammal Evolution, Charles Q. Choi, Live Science, September 10, 2014

Sunday, November 2, 2014

Cellular Energy Factories Were Once Deadly Energy Thieves

A bacterial tree of life, created by comparing gene sequences of modern bacteria species.
Mitochondria are cellular organelles which provide energy to cells in the form of ATP - adenosine triphosphate. This virtually universal, energy-dense biomolecule drives the chemical processes involved in "metabolism" - the breakdown (catabolism) and buildup (anabolism) of proteins and other essential biomolecules that make up living tissue and perform the necessary functions for sustaining life.

Mitochondria first emerged approximately 2 billion years ago, in what was a turning point for the advancement of complex life. That emergence has long been something of a mystery, one which we may now know the answer to.

We know that mitochondria are almost certainly descended from separate organisms because they possess a different set of genetic code from that contained in the nuclei of eukaryotic cells, which derive their names from the Latin words for "good kernel" because they all contain at least one DNA-enveloping cell nucleus.

Biologists have long believed that mitochondria first emerged when ancient host cells absorbed simple bacterial cells; these eventually evolved into the mitochondria found in virtually every modern eukaryotic cell. Thus, from the beginning, it was thought there was a symbiotic - mutually beneficial - relationship between the hosts and their resident mitochondria.

However, according to University of Virginia biologists Zhang Wang and Martin Wu, mitochondria are in fact descended from parasitic bacteria which originally preyed upon the cellular energy of early plant and animal ancestors, before evolving into the beneficial energy-producing organelles they are today.

Drs. Wang and Wu used state-of-the-art DNA sequencing to match mitochondrial DNA with that of its most closely-related bacterial cousins - 18 strains of bacterial parasites.

This indicates that mitochondria were almost certainly a type of bacterial parasite which stole ATP energy from their hosts. Only later did they begin switching the direction of ATP transport outward, thus providing the energy which would enable complex, multicellular life to emerge.

Source: "New U.Va. Study Upends Current Theories of How Mitochondria Began" press release, University of Virginia newsroom, October 16, 2014

Sunday, October 12, 2014

Rat Tickling and the Neuroscience of Emotions

Image: Patterns of emotionally-induced arousal and inhibition. Inhibition (purple) and arousal (red/yellow) within the lateral (outer region-top image pair) and medial (inner region-bottom image pair) regions of both brain hemispheres while human subjects experience emotions produced by personal memories. As indicated by changes in blood flow, inhibition is primarily derived from the outer (neocortical "self-control") regions - downward arrows, while excitation is primarily occurring in deep inner (subcortical "emotion-generating") regions. It is within these regions that Dr. Panksepp has traced seven neural pathways that, when stimulated, generate consistent emotional behaviors in all mammals. Source: Dr. Antonio Damasio/PLOS One. 
Within the dim, red-lit laboratory, a gentle, avuncular man in a white coat reaches into a glass tank and begins studiously tickling its inhabitant. His free hand holds a microphone, which amplifies and records the response - a high-pitched chortling which is, says the good doctor, the joyful giggling of a laboratory rat.

Meet Dr. Jaak Panksepp, colloquially referred to as the Rat Tickler. Here at Bowling Green State University, he has been pioneering the relatively new field of affective neuroscience.

For over five decades, Dr. Panksepp has meticulously mapped out neural circuits responsible for emotions, deep within the brains of humans and other animals. His findings may revolutionize psychiatry - providing powerful new tools to fundamentally alter the deepest instinctual drives and mental states shared by mammals and other animals, including birds, and perhaps to a lesser extent, reptiles, amphibians, fish and even crustaceans and insects.

He has discovered that these primary process systems arise from deep, ancient limbic brain structures, rather than from higher-order cognitive pathways of the neocortex - the brain's outer surface, where conscious thought, planning and judgements are processed.

These emotion-generating primary process systems are found within the same inner brain regions which regulate hormonal control of the body, via the brain's "thermostat" - the hypothalamus and pituitary gland.

The human brain, explains Dr. Panksepp, can be thought of as a nested hierarchy. Visualizing it in this way allows us to understand its layered organization and evolutionary development. His research shows that we have evolved a uniquely human cognitive (computational) mind atop a widely-shared affective (emotional-physical arousal states) mind. In general, the cognitive system uses neurotransmitters to process incoming sensory data, while the affective system uses neuromodulators to control overall brain states.

Unlike a neurotransmitter, a neuromodulator doesn't directly signal a single target neuron; instead, it spreads across a wide region, altering the activity of several neurons at once. Functionally, neuromodulators are thus able to act like chemical spigots - valves controlling the flow of neural signalling, altering the sensitivity of post-synaptic (signal-receiving) neurons or muscles to neurotransmitters, and thus altering signal strength, rhythm and timing.

The most abundant and powerful known neuromodulators include serotonin, dopamine, norepinephrine and acetylcholine. Because they circulate in the cerebrospinal fluid - the liquid bathing the brain and spinal cord, they can remain active for up to several minutes after release, altering widespread brain regions, including the cerebral cortex and deep neural hubs called the basal ganglia, central to learning and behavior. In this way, neuromodulators appear to underlie long-term effects upon mental and physical states - such as moods.

Higher up the heirarchy,  the basal ganglia produce secondary processes - learning, or creating memories, which can link sensory perceptions with emotional evaluations - feelings. This is the basis of conditioned learning - the formation of useful, survival-guiding memories.

At the third, topmost level, the neocortex uses life experiences to execute tertiary processes - higher-level computations which including thinking, ruminating, and planning. Here too, the forebrain and medial (middle) frontal cortex ideally provide control over emotional reactivity.

Certain neurochemicals and hormones produce highly predictable emotional-behavioral responses, by acting globally upon the brain, bringing several regions and various network functions under the "orchestration of one emotional conductor".  Among them are corticotropin releasing hormone (CRH) , which the hypothalamus secretes to start the chemical cascade of the stress response - more commonly known as the fight or flight response.

Three major neuromodulator systems are central to primary process circuitry, affecting the entire human brain and nervous system:

1. The ventral tegmental area (VTA), which supplies dopamine in the brain's "motivation circuit" - the medial forebrain bundle. This deep brain circuit provides pleasant sensations in the form of an excited expectancy - thus acting as a motivation center. Here, dopamine stimulation increases arousal in animals, which become more eager and inquisitive, engaging in exploratory behavior.

The MFB is part of the much larger mesolimbic system, running from the hypothalamus through the basal ganglia and medial frontal cortex. This is the brain's most important circuit for motivation, learning, and, pathologically, addictions. It's this pathway which is hijacked in addictions to drugs such as cocaine and amphetamines, which artificially increase dopamine levels in the synaptic clefts, the gaps between neurons, across which the chemical messengers known as neurotransmitters are delivered.

2. The dorsal raphe nucleus (DRN), a neural cluster in the midbrain and brainstem, which primarily supplies serotonin to the forebrain and limbic system. The serotonergic system is one of the brain's oldest neuromodulatory systems, primarily engaged in inhibition, opposing other neuromodulators, and thus inhibiting both sensory input and behavioral output. Serotonin is key to controlling impulsivity - behavior without forethought.

Laboratory animals low in serotonin are unable to restrain themselves from responding inappropriately. In humans, serotonin system dysfunction has been linked to an inability to suppress aggression. Serotonin is also critical for modulating and coping with stress, and emotional behavior in general. Impairment of the serotonergic system interferes with one's ability to deal with stressful situations.

3. The locus coeruleus (LC), a neural cluster located in the pons of the brainstem, is a region of the reticular activating system, with neurons that project into several regions of the limbic system - including the VTA - and cortex. The LC synthesizes the neuromodulator norepinephrine, used to regulate wakefulness, attentiveness and physiological responses to stress. It sends projections to the VTA (motivation), amygdala (fear, anger and other emotional processing, as well as salience discrimination - determining what specifically is important enough to our future survival for storing in memory), hippocampus (memory generation), thalamus (sensory processing and relaying) cerebral cortex (conscious thought, planning, sensory interpretation, self control) spinal cord and cerebellum (movement and balance coordination, possibly involved in language and learning), and thus also plays a significant role in learning.

Because of its wide effects, the LC system is central to attention, behavioral and cognitive control, memory, emotions, sleep cycles, and posture and balance. In conjunction with the hypothalamus, it also helps control responses to stress, specifically the fight or flight response. Increased sensitivity among neurons running from the LC to the amygdala is thought to be at the heart of learned fear disorders, such as post-traumatic stress disorder (PTSD).

While the dopamine system may induce general exploratory behavior, the LC-NA (noradrenaline is the older name for norepinephrine) system seems to promote goal-directed behavior, by influencing attentiveness.

Cognition - thought - is fed by accumulated life experiences, encoded as memories and factual knowledge. However, the primary processes - ancient affective states - are necessary to help generate these memories. New memories are encoded with the help of affective states, which enable animals to subjectively evaluate their life experiences.

In The Archaeology of Mind: Neuroevolutionary Origins of Human Emotions, Dr. Panksepp explains that these primary-process affects are "...ancient brain processes for encoding value - heuristics* of the brain for making snap judgements as to what will enhance or detract from survival, with rewarding or punishing effects."

"These brain functions provide selective advantages in that they effectively anticipate universal, future survival needs. Animals that had these capacities survived and bred with greater success.... Just imagine how useful pain is."

Dr. Panksepp's life work has been the discovery of seven such primary-process pathways - circuits which trigger distinct mental, physiological and behavioral patterns, including SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF, and PLAY. Because these pathways and their effects are both ubiquitous and fundamental (what evolutionary psychologists call evolutionarily homologous experiences), equivalent across different species of mammals, Dr. Panksepp spells them in capital letters.

To the pet owner, veterinarian or farmer, the notion that non-human animals cannot experience these emotions is patently absurd. Virtually all domesticated animals - dogs, cats, horses, pigs, cows, goats and even birds - display distinct personalities, temperaments and moods, including affection, loyalty, jealousy, fear, shame, pride, peevishness, anticipation, and many more. And mammals emit essentially the same emotionally expressive vocalizations as humans, including howls of rage, wails of grief, hoots or squeals of joy, and growls of anger. The generation of these sounds originates from the same brain region in every mammalian species. Despite all this, however, many modern scientists and corporate interests see animals as nothing more than simple stimulus-response boxes.

Dr. Panksepp's work is destined to permanently dispel such utilitarian illusions. He has been using a three-pronged approach to tracing these networks, homologous throughout the mammalian world: through direct electrical and chemical stimulation; through the rigorous study of instinctual behavior patterns; and through comparing human reports to (non-human) animal responses when these regions are stimulated, via electrodes or chemical injections.

He first became inspired to study neural correlates of emotions at the University of Massachusetts during the 1960s, while studying under Dr. Jay Trowill, who was experimenting with a new technique first introduced by Peter Milner and James Olds of McGill University - the insertion of electrodes into rat brains to create pleasant or unpleasant effects. In these experiments, after an electrode has been surgically implanted, a test rat is able to switch the electrical stimulation on or off with the press of a lever.

In one variation of such experiments, when a rat presses the control lever, the electrode stimulates regions of the medial forebrain bundle. After experiencing just a single stimulation, the experimental rats would immediately begin to repeatedly press the lever, stimulating their reward centers till they literally dropped from physical exhaustion.

However, activating the neural circuitry of the MFB through dopamine administration produces excited exploratory behavior similar to a search for food. Thus, this pathway seems to function as an instinctive motivation system, generating enthusiasm or expectancy, prompting animals to explore their environment for rewards. Amazingly, emotions can be switched on and off with a tiny electrical current.

In these experiments, since animals can activate or deactivate stimulation of each affect-generating regions, they indicate very clearly and consistently that they all dislike rage, fear, panic and grief, but they enjoy seeking, lust, care and play. And even invertebrates show some primitive affective responses: crayfish, for example, show an extreme liking for addictive substances like morphine and amphetamines, and bees display irritation when given inferior ingredients for their honey-making activities.

The primary process circuits are far more ancient than the earliest humans, who first emerged about two and a half million years ago, during the Pleistocene age.

They are at least as old as the divergence of the first mammals from their reptile ancestors.

These deep subcortical circuits encode the brain's basic emotional operating systems - a form of evolutionary memories.

Evolution tends to be parsimonious (stingy). Biological organisms don't constantly develop in radically new directions, or pass along traits which confer no survival value - natural selection ensures such wasteful development quickly fades out of existence. But features which do promote survival are passed on, as new species emerge from existing ones.

From an engineering standpoint, nearly all multicellular animals are basically tubes, optimized for food-harvesting, with a mouth at one end, and an anus at the other. Add wings, flippers, arms or legs, and you've simply created an eating machine that can harvest calories more quickly. Aside from one major apparently failed global experiment, the basic body plan hasn't changed.

Before the advent of modern genetic comparative analyses, scientists primarily used homologous traits - structures shared by diverse species - such as the jointed wings of a bat, the pectoral fins of a whale and the fingers of a human - to build phylogenic trees (ancestral charts). Such homologous traits are said to have been conserved - genetically preserved and passed down through the course of evolution. Among such conserved traits are a number of brain regions shared among vertebrates, particularly mammals.

Across the entire mammalian class, specific neural clusters and neurochemicals are shared, performing identical or nearly identical functions, depending upon each species' environmentally-determined survival needs. (There is greater detail available here for the particularly curious.)

These neural homologies began to emerge among the first chordates - half-a-billion-year-old creatures from which we descended, and among whose family we count ourselves. The first chordates (like the recently-rediscovered Pikaia) evolved in ancient Earth's oceans, and were so successful that some survive nearly unchanged to the present day. Among these living fossils are 32 known species of lancelets, which live half-buried in the sand of temperate and tropical shallows the world over. These segmented marine animals have "lance-shaped" bodies with sturdy, flexible notochords extending from head to tail, and a recognizable mouth for harvesting plankton.

The notochords would eventually evolve into into central nervous systems, which would branch out in ever-growing complexity from spinal cords. These would come to be encased in spinal columns, as animals incorporated the ancient oceans' abundant calcium salts into skeletal backbones.

Over time, the survival advantage of sense organs for sight, (and later taste, hearing and smell) required a concentration of neurons called ganglia in the creatures' foremost body region. As these early marine animals swam, this neural cluster could interpret incoming sensory data as efficiently as possible, enabling rapid navigation and food-harvesting.

As the stresses of environmental change reshaped their genes, ever more sophisticated chordates emerged - fish, amphibians, reptiles, birds and mammals. And as their sensory organs and locomotor systems grew in sophistication, so did their computational organs - their brains.

However, the parsimonious nature of evolution meant that certain features would get reused, rather than being re-engineered out of whole cloth. Because of this, humans share neural and neurochemical homologies with all mammals, including modern rodents, which superficially resemble our earliest mammalian ancestors.

But we share more than mere anatomical features with all Earth's mammals. In The Archaeology of Mind, Dr. Jaak Pansepp outlines what his five decades of experimentation have revealed: that we share our core emotions and drives with all mammals, and to a lesser extent, birds, reptiles and many other creatures.

We've inherited these traits for a good reason: emotions evolved to ensure survival. They serve as behavioral guides. Coupled with (and guiding the formation of) learned behaviors gleaned through experience, emotions prompt behaviors that bring comfort and reduce discomfort, increasing the odds of survival and reproduction. At heart, "affects" - the raw neural-hormonal responses and states which require cognition to be interpreted as emotions - produce the most basic behavior patterns - approach or avoidance.

The ancient circuitry which creates these affective states lies in the deepest, most evolutionarily ancient and conserved regions of the human brain, sprouting from atop the brainstem, which controls our most vital life functions, such as breathing, heartbeat swallowing and sleep-wake states. We know that these affects are limbically generated, because the behaviors continue even after decortication - the surgical removal of an animal's cortex.

These primal instinctive-emotional circuits are altered by experience, becoming more responsive (sensitization) or less so (habituation), depending upon both our experiences and our mental evaluations of them.

Dr. Panksepp's contribution to our understanding of affective neuroscience has been in charting how these seven emotional-behavioral circuits, when stimulated, produce virtually identical affects (though often differing effects) across every mammal species studied to date.

These seven neural systems lie deep below the level of the human cortex - the most recently-evolved, wrinkly outer layer - the seat of conscious thought, planning, evaluation, calculation and consideration. The primal drives and emotions to which they give rise are distinct from the homeostatic (biochemical balance-maintaining) affects such as hunger and thirst, and the purely sensory affects, which include disgust and various types of pain.

Says Dr. Panksepp, the infinite variety of subtle emotional shades we experienced are produced from a combination of these seven core affects, coupled with the unique melange of memories, cognition and bodily sensations each of us uses to interpret and shape them.

The seven core affective systems he has discovered to date are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF, and PLAY. Each of these seven primary-process emotional systems interacts with the others, with inhibitory or synergistic effects, as well as with the arousal systems, moderated by acetylcholine, norepinephrine, dopamine and serotonin, in special neural centers common to all vertebrates.

These neural attention/arousal subsystems are shared - primarily the circuitry concentrated in the brainstem - and are modulated by the neurohormones serotonin, norepinephrine, dopamine and acetylcholine - but overall, each affective circuit follows a distinct, specific path and neurochemistry, and each is shared by all mammalian brains.

As Dr. Panksepp explains: "Dopamine lies at the heart of... [the SEEKING system], controlling practically everything that organisms do. Its interactions with other brain regions are so extensive that it helps to facilitate most other emotional urges.

"likewise, norepinephrine, an even older system (since the cells are further down in the brain) facilitates attention during every kind of emotional arousal but more heavily so for euphoric feelings. Acetylcholine does the same, but often for more negative emotions."

Dr. Panksepp's work revises and expands upon the somewhat dated theory of Dr. Paul D. MacLean, an American neuroscientist who hypothesized in the 1960s that the modern brain evolved in three stages: a reptilian complex, a paleomammalian (ancient mammary-bearing animal) complex called the limbic system, and a neomammalian (new mammal) complex called the neocortex.

However, according to Dr. Panksepp, the circuitry reasonsible for these seven affective states - the "primary processes" - arise from the deepest, most ancient regions of the mammalian brain. They are hardwired - built into all mammalian brains, and not learned, constituting what he calls "ancestral memories".

The seven primary processes - raw emotional states - in turn control higher-order secondary processes - learning mechanisms such as associations. Both combine with tertiary processes - cognition - to create our conscious mind states. Affective states mix with and in turn moderate memories, complex ideas, reflections and subjective experiences.

Our uniquely individual gene patterns control the makeup of these seven primary-process circuits, leading to variability among us - emotional temperaments - which give rise with the force of habit to distinct personalities (which can, in turn, be altered by experience).

Dr. Panksepp describes these systems as "... SEEKING (expectancy), FEAR (anxiety), RAGE (anger), LUST  (sexual excitement), CARE (nurturance), PANIC/GRIEF (sadness), and PLAY (social joy). He addresses "...the primary-process nature of these systems,  and to a lesser extent, "...the secondary process (inbuilt emotional learning mechanisms) and the tertiary process (emotional thoughts and deliberations that are so evident in human experience)." He gives a brief summary of each of the seven affective systems as follows:
1. The SEEKING, or expectancy, system (discussed in Chapter 3) is characterized by a persistent exploratory inquisitiveness. This system engenders energetic forward locomotion—approach and engagement with the world—as an animal probes into the nooks and crannies of interesting places, objects, and events in ways that are characteristic of its species. This system holds a special place among emotional systems, because to some extent it plays a dynamic supporting role for all of the other emotions. When in the service of positive emotions, the SEEKING system engenders a sense of purpose, accompanied by feelings of interest ranging to euphoria. For example, when a mother feels the urge to nurture her offspring, the SEEKING system will motivate her to find food and shelter in order to provide this care. The SEEKING system also plays a role in negative emotions, for example, providing part of the impetus that prompts a frightened animal to find safety. It is not clear yet whether this system is merely involved in helping generate some of the behaviors of negative emotions, or whether it also contributes to negative feelings. For the time being, we assume it is largely the former, but that the positive psychological energy it engenders also tends to counteract negative feelings, such as those that occur during FEARful flight and the initial agitation of PANIC/GRIEF. For this reason, animals may actually find fleeing to be in part a positive activity, since it is on the most direct, albeit limited, path to survival.
2. The RAGE system (see Chapter 4), working in contrast to the SEEKING system, causes animals to propel their bodies toward offending objects, and they bite, scratch, and pound with their extremities. Rage is fundamentally a negative affect, but it can become a positive affect when it interacts with cognitive patterns, such as the experience of victory over one’s opponents or the imposition of one’s own will on others who one is able to control or subjugate. Pure RAGE itself does not entail such cognitive components, but in the mature multi-layered mammalian brain (Fig 1.4), it surely does.
3. The FEAR system (see Chapter 5) generates a negative affective state from which all people and animals wish to escape. It engenders tension in the body and a shivery immobility at milder levels of arousal, which can intensify and burst forth into a dynamic flight pattern with chaotic projectile movement to get out of harm’s way. If, as we surmised above, the flight is triggered when the FEAR system arouses the SEEKING system, then the aversive qualities of primary-process FEAR may be best studied through immobility “freezing” responses and other forms of behavioral inhibition, and reduced positive-affect, rather than flight.
4. When animals are in the throes of the LUST system (see Chapter 7), they exhibit abundant “courting” activities and eventually move toward an urgent joining of their bodies with a receptive mate (Figure 7.1), typically culminating in orgasmic delight—one of the most dramatic and positive affective experiences that life has to offer. In the absence of a mate, organisms in sexual arousal experience a craving tension that can become positive (perhaps because of the concurrent arousal of the SEEKING system) when satisfaction is in the offing. The tension of this craving may serve as an affectively negative stressor when satisfaction is elusive. LUST is one of the sources of love.
5. When people and animals are aroused by the CARE system (see Chapter 8), they have the impulse to envelop loved ones with gentle caresses and tender ministrations. Without this system, taking care of the young would be a burden. Instead, nurturing can be a profound reward—a positive, relaxed affective state that is treasured. CARE is another source of love.
6. When overwhelmed by the PANIC/GRIEF (also often termed “separation distress”) system (see Chapter 9), one experiences a deep psychic wound—an internal psychological experience of pain that has no obvious physical cause. Behaviorally, this system, especially in young mammals, is characterized by insistent crying and urgent attempts to reunite with caretakers, usually mothers. 
If reunion is not achieved, the baby or young child gradually begins to display sorrowful and despairing bodily postures that reflect the brain cascade from panic into a persistent depression. The PANIC/GRIEF system helps to facilitate positive social bonding (a
secondary manifestation of this system), because social bonds alleviate this psychic pain and replace it with a sense of comfort and belonging (CARE-filled feelings). For this reason, children value and love the adults who look after them. When people and animals enjoy secure affectionate bonds, they display a relaxed sense of contentment. Fluctuations in these feelings are yet another source of love.
7. The PLAY system (see Chapter 10) is expressed in bouncy and bounding lightness of movement, where participants often poke— or rib—each other in rapidly alternating patterns. At times, PLAY resembles aggression, especially when PLAY takes the form of wrestling. But closer inspection of the behavior reveals that the movements of rough-and-tumble PLAY are different than any form of adult aggression. Furthermore, participants enjoy the activity. When children or animals play, they usually take turns at assuming dominant and submissive roles. In controlled experiments, we found that one animal gradually begins to win over the other (becoming the top dog, so to speak), but the play continues as long as the loser still has a chance to end up on top a certain percentage of the time. When both the top dog and the underdog accept this kind of handicapping, the participants continue to have fun and enjoy this social activity. If the top dog wants to win all the time, the behavior approaches bullying. As we will see in Chapter 10, even rats clearly indicate where they stand in playful activity with their emotional vocalizations: When they are denied the chance to win, their happy laughter-type sounds cease and emotional complaints begin. The PLAY system is one of the main sources of friendship.
As Dr. Panksepp points out in his newest publication, "The goal of psychotherapy is affect regulation". Thus, his research is likely to be of enormous benefit in improving such therapeutic goals.

In a similar vein, researchers such as Emory University neurologist Dr. Helen Mayberg, have recently begun using electrical stimulation of targeted brain regions in hopes of helping patients whose depression is resistant to pharmacological treatments.

Dr. Mayberg's Deep Brain Stimulation technique may have alleviated severe depression in several patients, but Dr. Panksepp contends that this treatment is both figuratively and literally off the mark. He and his team are currently studying ways of addressing mood disorders through direct manipulation of the seven affective systems.

For example, Dr. Panksepp defines depression as an underactivated seeking urge, hobbled by excessive psychological pain. By directly altering the primary process neural circuits (such as the MFB), Dr. Panksepp hopes to counteract the psychological pain by strengthening the primitive seeking urge, in effect "amplifying eagerness to live". At this point, however, such technology is still very much in the experimental stages.

* heuristics are on-the-fly judgements based upon experience - commonly referred to as "best guesses", "common sense" or "rules of thumb".

Sources: Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals, Dr. Jaak Panksepp, September 07, 2011, Public Library of Science One; 
Discover Interview: Jaak Panksepp Pinned Down Humanity's 7 Primal Emotions, Pamela Weintraub, May 31, 2012, Discover Magazine; The Archaeology of Mind: Neuroevolutionary Origins of Human Emotions, Jaak Panksepp, Lucy Biven, Norton Series on Interpersonal Neurobiology, WW Norton and Company, 2012;
A Depression Switch? David Dobbs, April 2, 2006, New York Times

Tuesday, October 7, 2014

Ray Bradbury's "There Will Come Soft Rains" as interpreted by a Soviet animator

Director Nazim Tyuhladziev of the former Soviet state of Uzbekistan animated one of the most haunting science fiction short stories of all time - There Will Come Soft Rains, by the brilliant Ray Bradbury, my personal all-time favorite author (with the possible exception of Tolkein). 

The story tells of how, in the distant future, a completely automated house continues functioning, unable to understand that its charges have all died in a nuclear war. 

Friday, October 3, 2014

The cartography of emotion

Image: Finnish researchers have found specific patterns
of body sensations which correspond to each emotion.

Emotions, it is thought, evolved to provide animals with behavioral templates for their survival. They trigger changes in both the mind and body which help humans and other animals instinctively deal with environmental challenges.

Emotions change both our mental and physical states, enabling us to rapidly deal with danger, while also indicating potentially rewarding social interactions or rewards available in the environment.

The physical sensations arising from these biochemical changes are an important aspect of emotions. For example, while romantic love may elicit feelings of warmth and pleasure all over the body, deep sadness might give rise to a feeling of tightness in the chest.

In December 2013, researchers at Finland's Aalto University first attempted to systematically map the effects of emotions in the body.

Over 700 subjects from Finland, Sweden and Taiwan took part in the online study. The research team elicited varying emotional states in their participants, then invited them to use computer software to color regions of the body where they felt increased or decreased activity.

The researchers discovered that the strongest physical sensations come from the most common emotions, and the pattern of body sensations varies according to each emotion. However, these varying body sensation patterns are consistent in both eastern Asian and western European cultures, showing that emotions - and the body sensations to which they give rise - have biological origins distinct from any cultural origins.

Some theories suggest that conscious emotions follow sensations rather than the other way around - that the biochemical changes in our body lead to the conscious recognition that we are feeling a specific emotion.

It's believed that this line of research will have profound implications for our knowledge of the physical aspects of emotions, emotional disorders, and will provide new means of diagnosing such disorders.

Source: "Finnish research team reveals how emotions are mapped in the body", press release, Lauri Nummenmaa, et al, Aalto University, December 31, 2013

Thursday, October 2, 2014

Cracking the Code

RNA polymerases IV (green) and II (red) in the nucleus of an Arabidopsis
(rockcress) plant cell - Image: Dr. Olga Pontes, University of Indiana
One of evolution's deepest mysteries has been solved. Indiana University researchers have discovered how the effects of experience - environmental circumstances - can be handed down from parents to their offspring - without changes to DNA sequences.

According to IU biochemist Dr. Craig Pikaard, the secret to such epigenetic ("above the genes") inheritance lies in gene silencing patterns which can be preserved and passed down through generations. Instead of relying upon information hardwired by the DNA sequence, parent cells use chemical tags as guides for switching off the protein-manufacturing capability of specific DNA regions known as genes.

In essence, cells are essentially little more than tiny sacs of chemical reactions, all run by thousands of special proteins called enzymes, which float about the cytoplasm within your cells, conducting all the work these cells require. These molecules are tiny chemical-reaction machines, enabling your cells to conduct rapid chemical reactions every moment of your life, assembling and disassembling molecules when necessary, allowing cell growth and reproduction, among other functions.

In 1999, Dr. Pikaard discovered two gene-silencing plant enzymes: Pol IV and Pol V. These are RNA polymerases,  so-named because they are enzymes (denoted by the -ase suffix) used to create polymers (long chain molecules) of RNA molecules, the universal chemical blueprints which guide the assembly of proteins, the building blocks of life.

Dr. Pikaard's newest findings show how these enzymes shape plant development.

Genes aren't automatically silenced during normal DNA replication, but chemical markers can be added, providing a molecular memory which allows an offspring's cells to recognize which genes should be silenced. This allows modifications to be passed down without altering an organism's natural DNA sequence, just as installing a new program can alter a computer's functions without a change in its components.

Single-carbon (methyl) or double-carbon (acetyl) chemical tags can be added to or removed from DNA strands (chromatin), providing epigenetic information to the DNA sequence, which in turn guides RNA-assembly.

Short-interfering RNAs (siRNA) are tiny RNA molecules which guide methyl group attachment to DNA strands, deactivating specific gene sequences - the process called RNA-directed DNA methylation (RdDM).

This inheritance, called silent locus identity is controlled by two enzymes which work in tandem to control the chemical tagging responsible for epigenetic memory: histone deacetylase 6 (HDA6) which removes acetyl groups from histones (the protein spools around which chromatic strands wrap), and methyltransferase (MET1), used for DNA maintenance.

HDA6 and MET1 control the recruitment of Pol IV, the synthesis of siRNA and finally the process of RdDM, the final step in this form of gene silencing. The effects can be dramatic - sporadically-occurring diseases like cancer often seem to arise from such epigenetic changes to DNA.

Source: "Gene silencing instructions acquired through 'molecular memory' tags on chromatin - New work identifies machinery of epigenetic inheritance, relevant to development and cancer", press release, Stephen Chaplin, March 20, 2014, Indiana University

Sunday, September 14, 2014

Pure Magic

Nikola Tesla in his laboratory, 1899.

When people speak of longevity, I always joke that I intend to live to 200, for one simple reason.

For all its destructiveness, selfishness, and arrogance, the human race is endowed with the most amazing capacity - its creative ability. This unique attribute has given rise to masterpieces like Chartres Cathedral and the Large Hadron ColliderBeethoven's Ninth, and the Hubble Space Telescope.

To our early ancestors, all this would surely seem the fruits of powerful magic. And I, for one, can't wait to see mankind's next magic trick. Here are my favorites:

1. The PC
Since the Dark Age of DOS, a PC has provided me with the means of earning a living, and in the process become my most prized, multipurpose tool - a typesetter, photolab, publicist, accountant, recording studio, publisher, scout and personal secretary.

It's evolved significantly - my current home built PC functions as an alarm clock, fitness coach, interpreter, tutor, stereo, home theater and game center. I use it to design curricula, to write, illustrate, edit and publish books, blogs, brochures, business cards, posters, ads, and even songs and videos. And when the workday is done, it lets me shed my cares like a dusty overcoat, and lose myself in a movie or game. I heart PCs.

2. The Internet
The Japanese animation Doraimon recounts tales of a blue robotic cat from the future, equipped with an amazing bit of technology - the docodemo doa, or anywhere door. To me, this is a metaphor for the Internet.

Via the Internet's magic, I can now walk the halls of the most magnificent edifices in history, browse the Louvre, speak in tongues, earn a degree from Harvard, Oxford, or Columbia, chat face-to-face with friends across the planet, trace my family history, or order up a gene sequence as easily as a fresh pizza.

I can learn from history's most brilliant minds, and read wisdom as ancient as the earliest Sumerian cuneiform tablets or as fresh as captions streaming in real time across a live CNN broadcast. I can learn to dance, publish a best seller, or attend a conference without ever leaving my apartment, thanks to the doco demo door.

3. Google Maps
Feed it an address, and Google maps will instantly give step-by-step directions for travel on foot, or by public and private transport, with estimated arrival times and links to schedule, fare and route information. It's even possible to virtually walk the entire route via "street view" images, which comes in handy when one is traveling abroad. Access it on a cell phone, and I can track my progress toward my destination in real time. It's a spectacular innovation.

4. Facebook
Facebook is the greatest party in history. I have literally found everybody who ever meant anything to me - from my very first girlfriend to my old school chums and workmates from across the planet. Via Facebook, we can chat any time of day or night, via text, voice or video - or play mindless video games till dawn together, should the mood strike us.

5. The inflatable bicycle tire
To save money, stay in shape and reduce pollution, I ride a bicycle everywhere. It's given me a deep appreciation for something which remained beneath my notice for decades. Now every time I ride, I'm a bit amazed at the ingenuity that went into engineering the simple bicycle tire - mounted upon load-distributing spokes and sporting its clever little auto-sealing valve.

After inflating a flat, it feels oddly marvelous to glide effortlessly across the ground and to feel the tremendous difference in energy expenditure. This wonderful innovation was Irish inventor John Dunlop's 1888 gift to mankind.

6. The electric light bulb
I suspect that when Roald Dahl wrote Charlie and the Chocolate Factory, he was basing his main character, Mr. Willy Wonka, upon the Wizard of Menlo Park, who authored over two thousand patents worldwide, and gave the world its first electric power station, motion picture camera and sound recording.

Thomas Edison's amazing productivity was not just due to his brilliance, but also his Herculean patience. Forbes Magazine tells of how a reporter once asked him how it felt to spend years producing nothing but failed prototypes for a commercial light bulb, and his paradigm-shifting reply was reputedly: “I have not failed 10,000 times. I have not failed once. I have succeeded in proving that those 10,000 ways will not work. When I have eliminated the ways that will not work, I will find the way that will work.”

Perhaps Edison can be forgiven for indulging in a bit of self-aggrandization in the interest of marketing, but historians Robert Friedel and Paul Israel say that actually no less than twenty-two people invented various forms of electric lights before Edison filed his own 1878 patent. Chief among them was John W. Starr, who died shortly after filing an 1845 patent. And, says the Smithsonian, Edison and his team actually tested 1600 filaments of various types (including coconut fiber and human hair) before settling on carbonized fibers extracted from a folding bamboo fan he found in his factory.

7. Direct current
As if merely lighting up the world wasn't enough for Edison, he would soon create an entire electric power system to run his invention. The world's first power station, launched in 1882, would bring direct current power - and light! - to the masses.

Direct current is generally too expensive for large-scale long-distance distribution, so it's now primarily used in electronic devices, including the Integrated Circuit chips which manipulate the on and off states of binary code - the magnificent Lingua franca of the Digital Age.

8. Alternating current
One wonders if Edison's former employee and arch rival Nikola Tesla knew he was destined to reshape the world someday, by inventing the very lifeblood of our civilization. Try to visualize alternating current at work: electrons streaming across atoms, building speed to a climax, then slowing, and switching direction. The cycle repeats endlessly 50 to 60 times every second.

Tesla used AC to power induction motors - essentially the same variety which run most household appliances, such as vacuum cleaners and blenders. AC flows through copper coils wrapped around a cylindrical iron stator. This generates a magnetic field which induces a rotor inside to turn, running machines used by billions worldwide every day.

9. Binary code
The level of profound genius required to convert a machine's simple on or off states into a Lingua Franca capable of conveying everything from the entire works of Shakespeare to the launch control codes for artificial satellites is mind-boggling. Particularly when one realizes its inventor, the rather eccentric hypergenius Gottfried Leibniz, first devised the system over 300 years ago, in 1679 - based, no less, upon ancient Chinese mysticism. Beyond cool.

10. The internal combustion engine
This magic box harnesses the power of explosions to move cars, trucks and motorcycles. I remember first learning its inner workings in elementary school, daydreaming my way through the process - imagining spark plugs igniting oxygenated gasoline, and the explosions forcing pistons through cylinders hundreds of times every minute, rotating a crankshaft whose motion is ultimately transmitted via gears and axles to the wheels, propelling the vehicle forward. All hail the late, great Nikolaus August Otto.

Thursday, September 11, 2014

On the Recent Silence....

Apologies, kind readers. I have been rather busy as of late, because I am trying to enter graduate school at Harvard Extension to earn my masters in psychology.

My original degree is in journalism, with several certifications in IT, but I spent a year preparing for the general GRE, and earned the highest possible score for verbal reasoning (169) and was on the median (151) for quantitative reasoning. On the psychology GRE I scored in the 83rd percentile (90th for experimental psychology).

At any rate, if you're interested and/or able, you can get a tax write off by sponsoring me. Or if you like, you can purchase one or both of my books. Right now, I'm trying to raise the funds to attend the obligatory first semester on campus. My target for the semester is $17,000. After getting my foot in the door, I would then be eligible for federal funding and/or Harvard scholarships and grants.

You can also help by steering me toward any useful information on private funding.

Thanks for your time.