Bacteria's Protein-Based 'Living Wires' Allow Electron Transference throughout Protein by use of Electricity

Hugging Hemes Help Electrons Hop 
by Mary Beckman for PNNL News Richland WA (SPX) Jan 23, 2014

Numbered heme groups (in color) lie within MtrF protein's framework (in gray) and shuttle electrons from one end of the protein to the other.

Researchers simulating how certain bacteria run electrical current through tiny molecular wires have discovered a secret Nature uses for electron travel. The results are key to understanding how the bacteria do chemistry in the ground, and will help researchers use them in microbial fuel cells, batteries, or for turning waste into electricity.

Within the bacteria's protein-based wire, molecular groups called hemes communicate with each other to allow electrons to hop along the chain like stepping stones. The researchers found that evolution has set the protein up so that, generally, when the electron's drive to hop is high, the heme stepping stones are less tightly connected, like being farther apart; when the drive to hop is low, the hemes are more closely connected, like being closer together. The outcome is an even electron flow along the wire.

This is the first time scientists have seen this evolutionary design principle for electron transport, the researchers reported Jan. 2 in Proceedings of the National Academy of Sciences Early Edition Online.

"We were perplexed at how weak the thermodynamic driving force was between some of these hemes," said geochemist Kevin Rosso of the Department of Energy's Pacific Northwest National Laboratory. "But it turns out those pairs of hemes are essentially hugging each other. When the driving force is strong between hemes, they are only shaking hands. We've never seen this compensation scheme before, but it seems that the purpose is to allow the protein to transfer electrons with a steady flow along heme wires."

Living Wires Certain bacteria breathe using metal like people use oxygen. In the process, these bacteria steal electrons from carbon and ultimately transfer the electrons to metals or minerals in the ground. They do this by conducting electricity along molecular wires built into proteins, moving internal electrons to the outside of their cells. Researchers hope to use these bacteria in little biologic batteries or fuel cells.

But a living wire is not the same as those that make up our powerlines. Electrons in powerlines hurtle down the wire, moving smoothly from metal atom to metal atom. Electrons traveling in a living wire must get from one complex heme group to the next. The hemes are situated within a protein, and not all hemes are made the same.

Some hemes hold onto electrons tightly and others let electrons slip away easily. Depending on how the hemes are lined up, this can create energetic hills that electrons have a hard time climbing over, or energetic valleys that electrons easily march across.

Some hemes, such as those that carry oxygen in people's red blood cells, are well-studied. The hemes and proteins creating a current in bacteria, though, have only been coming to light within the last few years. Recently, researchers figured out what a particular protein-MtrF-that makes up a molecular wire looks like, but that information alone is not enough to determine how the electrons traverse the chain of internal heme groups.

So, armed with the structure of the protein, Rosso and colleagues Jochen Blumberger and Marian Breuer from the University College London used high-powered computers to simulate the positions and movement of the hemes in MtrF and how they transfer electrons between themselves.

Electron Crossroads
Using resources at both the UK's High Performance Computing Facility and EMSL, the Environmental Molecular Sciences Laboratory at PNNL, the team first modeled the average position of the 10 hemes within MtrF. Eight of the hemes run down the center of the protein. The remaining two hemes branch off the main eight, creating a four-heme road that crosses the middle of the protein.

Because hemes have to pass electrons to each other, the team examined them in pairs. The team found that MtrF arranges its heme pairs in one of three ways: perpendicular to each other, side-by-side, or stacked on top of each other. Each arrangement positions the hemes at different distances from and orientations to each other.

Then the team gauged how urgently an electron wants to get from one heme to the next by determining the theoretical "Gibbs free energy" between the pairs. This value is an indicator of the driving force of the electrons.

The team found that instead of a smooth ride through the protein, electrons lurch through hemes: Sometimes the driving force makes the electrons march across a valley and the electrons move quickly. In other pairs the electrons face a hill, and electron travel gets delayed.

Mapping how tightly hemes couple to each other along with the driving force values, the team found that hemes were less tightly coupled when electrons enjoyed traipsing across a valley and more tightly coupled when electrons had to slog uphill.

"The computer simulations allowed us to break the wire down into how each step is possible and how fast each step is. Then we saw that the protein arranges its hemes in weak and strong couplings to compensate for the energetic hills and valleys," said Rosso. "This is one way to make the electron hops consistent to efficiently get them where they need to go."

This compensation scheme led the team to wonder why the hills and valleys are there in the first place.

"We think the variation in driving force between the hills and the valleys helps the protein interact with other components in the environment," said Rosso. The tops of the hills could be exit points to higher energy electron acceptors in the environment, such as molecules that shuttle electrons elsewhere.

Scientists don't yet know how multiple heme proteins-including others beyond MtrF-work in concert to make these molecular wires connect end-to-end, but the results give hints as to which hemes are possible entry and exit points in MtrF. So the results also give clues to how multiple proteins might be connected.

This work was supported by the Department of Energy Office of Science. Support for use of the UK's High Performance Computing Facility was provided by the UK's Engineering and Physical Sciences Research Council. Additional support was provided by the Royal Society.

Reference: Marian Breuer, Kevin M. Rosso, and Jochen Blumberger. Electron flow in multiheme bacterial cytochromes is a balancing act between heme electronic interaction and redox potentials, Proc Natl Acad Sci U S A, Early Edition online January 2, 2014. doi:10.1073/pnas.1316156111.

Measuring Schrodinger's Cat - Pet Gently, then Snap a Picture that Collapses the WaveFunction

Peeking into Schrodinger's Box by Staff Writers Rochester NY (SPX) Jan 23, 2014

'A schematic of the experimental setup using a HeNe laser, lenses, beam-splitters, wave-plates, a fan-out hologram and other tools. Light can be thought of as a spiral and the orbital-angular-momentum quantum number describes how "twisted" this spiral is. The weak measurement setup shows how this spiral is "untwisted" before it is measured. Image courtesy M. Malik/Nature Communications'.

Until recently measuring a 27-dimensional quantum state would have been a time-consuming, multistage process using a technique called quantum tomography, which is similar to creating a 3D image from many 2D ones. Researchers at the University of Rochester have been able to apply a recently developed, alternative method called direct measurement to do this in a single experiment with no post-processing.

The work is of interest because fast, accurate and efficient methods for characterizing high-dimensional states like this could be central in developing high security quantum communications systems, as well as to probe our fundamental understanding of quantum mechanics.

The work was published this week in Nature Communications by a team of researchers from the University of Rochester and the University of Glasgow. In the paper they demonstrate direct measurements of the quantum state associated with the orbital-angular momentum.

"Our work shows that direct measurement offers an exciting alternative to quantum tomography," said Robert Boyd, Professor of Optics and Physics at the University of Rochester and Canada Excellence Research Chair in Quantum Nonlinear Optics at the University of Ottawa.

"As the field of quantum information continues to advance, we expect direct measurement to play an increasingly important role in this." Boyd added that although it is unclear exactly how much more efficient direct measurement is compared to quantum tomography, the lack of post-processing is a major factor in speeding-up direct measurements.

The direct measurement technique offers a way to directly determine the state of a quantum system. It was first developed in 2011 by scientists at the National Research Council Canada, who used it to determine the position and momentum of photons.

Last year, a group of Rochester/Ottawa researchers led by Boyd showed that direct measurement could be applied to measure the polarization states of light. The new paper is the first time this method has been applied to a discrete, high dimensional system.

Such direct measurements of the wavefunction might have appeared to be ruled out by the uncertainty principle - the idea that certain properties of a quantum system could be known with precision only if other properties were known poorly. However, direct measurement involves a "trick" that makes it possible.
Direct measurements consists of two types of measurements performed one after the other, first a "weak" measurement followed by a "strong" measurement.

In quantum mechanics the act of measuring a quantum state disturbs it irreversibly, a phenomenon referred to as collapse of the wavefunction. The trick lies with the first measurement being so gentle that it only slightly disturbs the system and does not cause the wavefunction to collapse.

"It is sort of like peeking into the box to see if Schrodinger's cat is alive, without fully opening the box," said lead author Dr. Mehul Malik, currently a post-doctoral research fellow at the University of Vienna and who was a Ph.D. in Boyd's group when the work was performed.

"The weak measurement is essentially a bad measurement, which leaves you mostly uncertain about whether the cat is alive or dead.

It does, however, give partial information on the health of the cat, which when repeated many times can lead to near certain information as to whether the cat is alive or dead." Malik adds that the beauty of the weak measurement is that it does not destroy the system, unlike most standard measurements of a quantum system, allowing a subsequent measurement-the "strong" measurement of the other variable.

This sequence of weak and strong measurements is then repeated for multiple identically prepared quantum systems, until the wave function is known with the required precision.

Ph.D. student Mohammad Mirhosseini was also part of the Rochester team. Other collaborators included Professor Miles Padgett and Martin Lavery from the University of Glasgow, UK, and Dr. Jonathan Leach, from Heriot-Watt University, Edinburgh, UK.

Dynamic Systems, like Nature, are Fractal

Probing the Edge of Chaos by Staff Writers Heidelberg, Germany (SPX) Mar 03, 2014

File image: central limit theorem.

The edge of chaos-right before chaos sets in-is a unique place. It is found in many dynamical systems that cross the boundary between a well-behaved dynamics and a chaotic one.

Now, physicists have shown that the distribution-or frequency of occurrence-of the variables constituting the physical characteristics of such systems at the edge of chaos has a very different shape than previously reported distributions.

The results, by Miguel Angel Fuentes from the Santa Fe Institute in New Mexico, USA, and Universidad del Desarrollo, Chile, and Alberto Robledo from the National Autonomous University of Mexico, Mexico City, are published in EPJ B. This could help us better understand natural phenomena with a chaotic nature.

In probability theory, the central limit theorem was first developed by an 18th century French mathematician named Abraham de Moivre.

It applies to independent random physical quantities or variables, each with a well-defined expected value and well-defined way of varying. This theorem states that once iterated a sufficiently large number of times, these variable physical quantities will be approximately distributed along a central limit-also referred to as the attractor. In chaotic and standard random systems, such distribution is in the shape of a bell curve.

Now, new central limit theorems are emerging for more complex physical processes, such as natural phenomena. In this study, the authors took existing knowledge of the specific position of the attractor at the edge of chaos.

To do so, they employed a mathematical formula called the logistic map as a particular example of the dynamic system under study. They found that the distribution of physical properties of such dynamic systems at this specific point at the edge of chaos has a fractal structure not previously known.

M. A. Fuentes and A. Robledo (2014), Sums of variables at the onset of chaos, European Physical Journal B, DOI 10.1140/epjb/e2014-40882-1

The Human Brain Project

Thinking it through: Scientists seek to unlock mysteries of the brain  
by Staff Writers Chicago IL (SPX) Feb 20, 2014

This is a group of neurons. Image courtesy EPFL/Human Brain Project.

Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to this challenge, we will gain profound insights into what makes us human, develop new treatments for brain diseases, and build revolutionary new computing technologies that will have far reaching effects, not only in neuroscience.

Scientists at the European Human Brain Project-set to announce more than a dozen new research partnerships worth Eur 8.3 million in funding later this month-the Allen Institute for Brain Science, and the US BRAIN Initiative are developing new paradigms for understanding how the human brain works in health and disease.

Today, their international and collaborative projects are defined, explored, and compared during "Inventing New Ways to Understand the Human Brain," at the 2014 AAAS Annual Meeting in Chicago.

Brain Simulation, Big Data, and a New Computing Paradigm

Henry Markram from the Ecole Polytechnique Federale de Lausanne (EPFL), in Switzerland, where the Human Brain Project is based, describes how the project will leverage available experimental data and basic principles of brain organization to reconstruct the detailed structure of the brain in computer models. The models will allow the HBP to run super-computer based simulations of the inner working of the brain.

"Brain simulation allows measurements and manipulations impossible in the lab, opening the road to a new kind of in silico experimentation," Markram says.

The data deluge in neuroscience is resulting in a revolutionary amount of brain data with new initiatives planning to acquire even more. But searching, accessing, and analyzing this data remains a key challenge.
Sean Hill, also of EPFL and a speaker at AAAS, leads The Neuroinformatics Platform of the Human Brain Project (HBP). In this scientific panel, he explains how the platform will provide tools to manage, navigate, and annotate spatially referenced brain atlases, which will form the basis for the HBP's modeling effort-turning Big Data into deep knowledge.

The Neuroinformatics Platform will bring together many different kinds of data. University of Edinburgh's Seth Grant, a key member of the HBP, describes how he is deriving new methods to decode the molecular principles underlying the brain's organization, such as how individual proteins assemble into larger complexes.
As Grant explains in Chicago, this has important practical applications as many mutations in schizophrenia and autism converge on these so-called supercomplexes in the brain.

As we understand more and more about the way the brain computes we can apply this knowledge to technology. Karlheinz Meier, of Heidelberg University in Germany and a speaker at AAAS, outlines how he is working to create entirely new computing systems as part of the HBP. These Neuromorphic Computing Systems will merge realistic brain models with new hardware for a completely new paradigm of computing-one that more closely resembles how the brain itself processes information.

"The brain has the ability to efficiently perform computations that are impossible even for the most powerful computers while consuming only 30 Watts of power," Meier says.

Brain: Get Ready For Your Close-up

At AAAS, Christof Koch lays out another ambitious, 10-year plan from the Allen Institute for Brain Science: to understand the structure and function of the brain by mapping cell types from mice and humans with computer simulations and figuring out how the cells connect, and how they encode, relay, and process information. The project, Koch says, promises massive, multimodal, and open-access datasets and methodology that will be reproducible and scalable.

At Harvard University, George Church is participating in the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which aims to map every neuron in the brain with rapidly advancing technologies. At AAAS, he describes progress on new tools for measurements of brain cell development, connectivity, and functional state dynamics in rodent and human clinical samples.

What do all of these projects have in common? They seek to help find some of the most elusive answers known to man: what makes us human, how does the brain function, what causes neurological and mental illness, and, most importantly, how can we treat or cure these afflictions?

Human Brain Project

The goal of the HBP is to build a completely new Information and Communications Technology infrastructure for neuroscience and for brain-related research in medicine and computing, catalyzing a global collaborative effort to understand the human brain and its diseases and ultimately to emulate its computational capabilities.
The 10-year, 1 billion Euro project funded by the EU's FET Flagship Program was launched on October 1, 2013, and involves 80 leading universities and research institutions from 22 European countries as well as the US, Canada, Japan, and China.

Later this month (February 2014), the HBP and the EU will announce more than a dozen new research partnerships worth up to Eur 8.3 million based on the results of competitive calls for proposals opened in October, 2013, and currently in the final stages of selection. Research proposals cover topics from cognitive architectures to virtual robotic environments to the theory of multiscale circuits. The winners become full members of the global Human Brain Project Consortium.

A key aspect of the HBP is the use of supercomputer-based modeling. As supercomputers move towards the exascale and the quality of our models improves, HBP models will make it possible to conduct in silico experiments impossible in the lab.

The project has a strong focus on applications in computing and in medicine. In computing, the project will transfer simplified versions of its brain models into novel "neuromorphic computing systems" with capabilities completely lacking in current computing technology.

In medicine, the project will create tools making it possible to mine large volumes of anonymized patient data, to identify the "biological signatures" of neurological and psychiatric disease, and ultimately to build computer models of specific conditions. Such models will facilitate the screening of new treatments, speeding up drug development, and encouraging urgently needed investment in Central Nervous System research.

IBEX Helps Paint Picture of the Magnetic System Beyond the Solar Wind

by Karen C. Fox for Goddard Space Flight Center Greenbelt MD (SPX) Feb 16, 2014

A model of the interstellar magnetic fields - which would otherwise be straight -- warping around the outside of our heliosphere, based on data from NASA's Interstellar Boundary Explorer. The red arrow shows the direction in which the solar system moves through the galaxy. Image courtesy NASA/IBEX/UNH.

Understanding the region of interstellar space through which the solar system travels is no easy task. Interstellar space begins beyond the heliosphere, the bubble of charged particles surrounding the sun that reaches far beyond the outer planets. Voyager 1 has crossed into this space, but it's difficult to gain a complete global picture from measurements in only one direction.

Spacecraft data in the past five years from near Earth and cosmic ray observations have painted a better picture of the magnetic system that surrounds us, while at the same time raising new questions. Scientists are challenging our current understanding in a new study that combines observations of massively energetic cosmic ray particles streaming in from elsewhere in the Milky Way along with observations from NASA's Interstellar Boundary Explorer, or IBEX.

The data sets show a magnetic field that is nearly perpendicular to the motion of our solar system through the galaxy. In addition to shedding light on our cosmic neighborhood, the results offer an explanation for a decades-old mystery on why we measure more incoming high-energy cosmic rays on one side of the sun than on the other. The research appears in the Feb. 13, 2014, issue of Science Express.
"It's a fascinating time," said Nathan Schwadron, of the University of New Hampshire in Durham and first author on the paper. "Fifty years ago, we were making the first measurements of the solar wind and understanding the nature of what was just beyond near-Earth space. Now, a whole new realm of science is opening up as we try to understand the physics all the way outside the heliosphere."

The heliosphere is formed as the constant stream of particles from the sun's solar wind flows outward in all directions until it slows down to balance the pressure from the interstellar wind. The only information gathered directly from the heart of this complex boundary region is from NASA's Voyager mission. Voyager 1 entered the boundary region in 2004, passing beyond the termination shock where the solar wind abruptly slows down. Voyager 1 crossed into interstellar space in 2012.

IBEX, which orbits Earth, studies these regions from afar. The spacecraft detects energetic neutral atoms that form from interactions at the heliosphere's boundaries - an area that holds fascinating clues to what lies beyond.

These interactions are dominated by electromagnetic forces. The incoming particles from the galaxy are made up of negatively-charged electrons, positively-charged atoms called ions, neutral particles and dust. Charged particles are forced to travel along the magnetic field lines that snake throughout space.

Sometimes, a charged particle collides with a neutral atom at the outskirts of the heliosphere and captures an electron from the neutral atom. After stealing the electron, the charged particle becomes electrically neutral and speeds off in a straight line.

Some of these fast neutral particles stream into the inner solar system and reach IBEX's detectors. Depending on the speed and direction of those neutral particles, scientists can determine information about the atoms and magnetic field lines involved in the original collision.

In 2009, IBEX scientists presented research showing an uneven distribution of neutral atoms. There was a ribbon along the heliospheric boundaries sending a preponderance of neutral atoms toward IBEX.

Researchers wondered if this shape might also relate to an unevenness seen in cosmic rays. On Earth, we measure more cosmic rays - particles that stream in from the rest of the galaxy at 99% the speed of light - coming in from near the tail side of the heliosphere than from the other side. Teasing out the source and paths of incoming cosmic rays isn't easy as the rays gyrate around magnetic field lines both inside and outside our heliosphere before colliding with other particles in Earth's atmosphere, giving a shower of secondary particles that, in turn, are what we detect. To complicate things further, the heliosphere is moving through the galaxy.

"At some level, it's like trying to determine the wind direction when you're riding a bike very quickly and the wind isn't particularly strong," said Eric Christian, the IBEX project scientist at NASA's Goddard Space Flight Center in Greenbelt, Md., and a co-author on the paper. "There's some effect from the wind, but it's small and hard to measure."

To see if the IBEX data related to the cosmic ray observations, Schwadron used IBEX data to build a computer model of what the interplanetary magnetic field would look like around the heliosphere. Without the heliosphere, the field lines would be straight and parallel.

"But the heliosphere is kind of like an egg sitting in the middle of all these magnetic field lines," said Schwadron. "The field lines have to distort themselves around that."

With this model in hand, he simulated how the heliosphere would affect the cosmic rays. He assumed that the rays came in to the heliosphere evenly from everywhere in space, but allowed them to be warped based on the local magnetic geometry. The simulations showed a non-uniform distribution of cosmic ray particles that jibed well with the unevenness seen in observations.

"The analysis of this important paper strongly correlates with the theoretical view of the heliosphere from the numerical model developed by our team, which uses IBEX observations to derive the interstellar magnetic field direction," said Nick Pogorelov, a space scientist at the University of Alabama in Huntsville, who works with IBEX data.

"It shows that the heliopause that separates solar and interstellar plasmas is very long, maybe 2 trillion miles in the downwind direction, and therefore may affect the transport of high-energy cosmic rays toward the solar system."

Unfortunately, this doesn't prove that the heliosphere and the interstellar magnetic field are exclusively responsible for the cosmic ray mystery. However, this research shows that the magnetic configuration of our neighborhood does offer a potential answer.

Moreover, the agreement between what's seen in the cosmic ray data and by IBEX provides outside confirmation of IBEX's results of what the magnetic fields outside our heliosphere look like. That's an interesting piece of the puzzle, when compared with Voyager 1's measurements, because the Voyager 1 data provide a different direction for the magnetic fields just outside our heliosphere.

This doesn't mean that one set of data is wrong and one is right, says Schwadron. Voyager 1 is taking measurements directly, gathering data at a specific time and place; IBEX gathers information averaged over great distances, so, there is room for discrepancy.

Indeed, that discrepancy can be used as a clue. Understand why there's a difference between the two measurements and we gain additional information. More IBEX observations and more Voyager observations will keep coming in. As with all research, more data will help unravel the picture and soon we will learn even more about how we fit into the rest of the universe.

Solving a physics mystery: Those 'solitons' are really vortex rings

by Staff Writers Seattle WA (SPX) Feb 07, 2014
 

An example of a vortex ring, also called a toroidal bubble, which dolphins create under water. The concept of vortex rings lies at the heart of new University of Washington physics research.   Image by Paul Nylander (http://bugman123.com)"

The same physics that gives tornadoes their ferocious stability lies at the heart of new University of Washington research, and could lead to a better understanding of nuclear dynamics in studying fission, superconductors and the workings of neutron stars.

The work seeks to clarify what Massachusetts Institute of Technology researchers witnessed when in 2013 they named a mysterious phenomenon - an unusual long-lived wave traveling much more slowly than expected through a gas of cold atoms. They called this wave a "heavy soliton" and claimed it defied theoretical description.

But in one of the largest supercomputing calculations ever performed, UW physicists Aurel Bulgac and Michael Forbes and co-authors have found this to be a case of mistaken identity: The heavy solitons observed in the earlier experiment are likely vortex rings - a sort of quantum equivalent of smoke rings.

"The experiment interpretation did not conform with theory expectations," said Bulgac. "We had to figure out what was really happening there. It was not obvious it was one thing or another - thus it took a bit of police work."

A vortex ring is a doughnut-shaped phenomenon where fluids or gases knot and spin in a closed, usually circular loop. The physics of vortex rings is the same as that which gives stability to tornadoes, volcanic eruptions and mushroom clouds. (Dolphins actually create their own vortex rings in water for entertainment.)
"Using state-of-the-art computing techniques, we demonstrated with our simulation that virtually all aspects of the MIT results can be explained by vortex rings" said Forbes, an UW affiliate professor who in January became an assistant professor of physics at Washington State University.

He said the simulations they used "could revolutionize how we solve certain physics problems in the future," such as studying nuclear reactions without having to perform nuclear tests. As for neutron stars, he said the work also could lead to a better understanding of "glitches," or rapid increases in such a star's pulsation frequency, as this may be due to vortex interactions inside the star.

"We are now at a cusp where our computational capabilities are becoming sufficient to shed light on this longstanding problem. This is one of our current directions of research - directly applying what we have learned from the vortex rings," Forbes said.

The computing work for the research - one of the largest direct numerical simulations ever - was performed on the supercomputer Titan, at the Oak Ridge Leadership Computing Facility in Tennessee, the nation's most powerful computer for open science. Work was also performed on the UW's Hyak high-performance computer cluster.

Biggest Teahupoo Ever,

The Secret Life of Vortices: Evolution and Destruction of Vortical Flows

Knots and Fluid Flow - Finding Patterns within Turbulence

Could Knots Unravel Mysteries of Fluid Flow?

Irvine Lab

A trefoil vortex knot in water generated by a hydrofoil.

By: Natalie Wolchover

December 9, 2013

Spaghetti-thin shoelaces, sturdy hawsers, silk cravats — all are routinely tied in knots. So too, physicists believe, are water, air and the liquid iron churning in Earth’s outer core. Knots twist and turn in the particle pathways of turbulent fluids, as stable in some cases as a sailor’s handiwork. For decades, scientists have suspected the rules governing these knots could offer clues for untangling turbulence — one of the last great unknowns of classical physics — but any order exhibited by the knots was lost in the surrounding chaos.

Now, with deft new tools at their fingertips, physicists are beginning to master the art of tying knots in fluids and other flowable entities, such as electromagnetic fields, enabling controlled study of their behavior. “Now that we have these knots, we can measure the shape of them in 3-D; we can look at the flow field around them,” said William Irvine, a physicist at the University of Chicago. “We can really figure out what the rules of the game are.”

Knots and linked loops exist in turbulent fluids like Earth’s outer core because they arise when a rotation coincides with a flow. (As the fluid rotates, the particle pathways, or “streamlines,” get dragged around and entangled in an effect similar to tying a shoelace.) Investigating knotted fluids both on paper and in the lab could provide a much richer picture of how these tangles, once formed, affect the future evolution of the fluids. The researchers say this new means of probing fluid flow could eventually advance the scientific understanding of the plasma rising off the surface of the sun, thermonuclear fusion, Earth’s interior and atmosphere, and other systems embroiled in turbulence.

“This is all a realization of this dream of understanding fluids in terms of the knots and links of the streamlines,” said Randy Kamien, a professor of physics and astronomy at the University of Pennsylvania.

Illustrations of knots and links, including a trefoil knot, top left, in an 1869 paper by Lord Kelvin on his knotted vortex theory of atoms. Related Video: Knot Possible?

The dream began in the 1860s with an ingenious knot theory of nature. Lord Kelvin proposed that atoms were knotted vortexes swirling in the ether, an invisible, fluidlike medium believed at the time to fill space. One element would be the simplest knot, called a trefoil, another a figure-eight knot, and so on — and none could transform into another. Though incorrect, Kelvin’s idea spawned the branch of mathematics known as knot theory and ultimately led to the realization that knots do more than passively form in fluids; they can have a pivotal, though as yet poorly understood, influence on turbulent fluid dynamics. In seminal work published in 1969, Keith Moffatt, then a young Cambridge University lecturer, proved that the measure of the total knottedness and linkage in ideal fluids — ones, like liquid helium, that lack viscosity — stays constant over time. In viscous fluids, this measure, called “helicity,” fluctuates, and knots can transform or unravel. But scientists still don’t know when and why helicity dissipates.

“There is a vast literature about what happens to knottedness in fluids, but it has been really hard to do experiments for a long time,” Irvine said. “It wasn’t until recently that we got these great tools for making and measuring things in 3-D, which is essential for knots.”

Earlier this year, Irvine’s team used water displacing objects called hydrofoils, created through 3-D printing, to fashion a trefoil knot out of a water vortex — the first vortex knot ever created in the lab. Using lasers, Kamien’s group constructed a knotlike structure in liquid crystals, the self-aligning fluids found in LCD television screens. And a third group — led by Mark Dennis, a theoretical physicist at the University of Bristol in the United Kingdom — tied knots in filaments of darkness swirling inside laser beams.

Alongside the experimental advances, researchers have also formulated new mathematical descriptions of knotted fluids and fields that can be analyzed on paper rather than in the lab.
Electromagnetic fields — entities that fill space and oscillate at different frequencies, some of which our eyes perceive as light — are mathematical solutions to a set of laws known as Maxwell’s equations. As reported in October in Physical Review Letters, Irvine and his colleagues Hridesh Kedia, Iwo Bialynicki-Birula and Daniel Peralta-Salas discovered a large class of solutions in which the contours of the electromagnetic fields, called “field lines,” twist and turn in knots.

A static, knotted electromagnetic field was derived in the 1990s, but “the new work is much more general,” said Moffatt, now a professor emeritus of mathematical physics at Cambridge. “They provide a technique for finding a really huge variety of knots.”

Irvine and coauthors will show in forthcoming work that there are corresponding knotted solutions to Euler’s equations, which govern ideal fluids. Because they have zero viscosity, these fluids flow perfectly smoothly, much like the light fields studied by the researchers. “It illustrates that we can be talking about very different physical systems with the same sorts of solutions,” Dennis noted. This equivalence means that if physicists discover the principles behind knots in Earth’s core, the same rules should apply to the tangled vortexes near an airplane wing.

A Knotty Picture

To visualize a knotted electromagnetic field, imagine three-dimensional space partitioned into doughnut-shaped tori of a continuous range of sizes, nested like Russian dolls. Collections of field lines (shown above in orange and blue) form the surface of each torus. In the trefoil knot field, each line wraps twice around the perimeter of the torus and three times through the center. As a result, any two lines on the same torus are knotted, and any two lines from different tori are knotted too. “It gives you a way of filling space with knots,” Irvine said. Then, as the field propagates through space and time, “these knots travel with the light.” (Illustration: Irvine Lab)

The knotted light fields that Irvine and his colleagues derived on paper may be realizable experimentally, he said, within a tightly focused and polarized laser beam. By shining the knotted beam onto another material, such as plasma, it should also be possible to “transfer the knottedness onto that thing,” he said, enabling controlled study of knots in a range of settings.

At present, almost nothing is experimentally proven about how knots in fluids and fields evolve over time despite decades of speculation and extensive computer simulations.

“Suppose William [Irvine] made two trefoil knots in a fluid and shot them at each other,” Kamien said. “What do they do? How do they interact? That’s completely beyond the scope of what we understand.” The answers to these seemingly simple questions, he added, are central to “how fluids work.”

For starters, when do knots unravel and when do they not? Moffatt proved that helicity stays constant in zero-viscosity fluids — a law of nature analogous to the conservation of energy in frictionless systems. But just as friction saps energy from a car, particle collisions suck helicity out of viscous fluids like water and plasma. “We know helicity is not exactly conserved, but how is it not exactly conserved?” Kamien asked. “Nobody really knows.”

Gary A. Glatzmaier, Los Alamos National Laboratory, U.S. Department of Energy
A supercomputer model of flow patterns in Earth’s liquid iron outer core. The fluid’s complex topology is believed to play a central role in the “dynamo effect,” which generates the planet’s magnetic field.

The most pressing question is what happens when knotted or linked vortices in a viscous fluid cross and separate — a common process called reconnection. Some researchers hypothesize that link or knot helicity is converted into “twist helicity,” or faster swirling of the vortices, keeping the total helicity constant. However, preliminary work by Moffatt and Yoshifumi Kimura, a professor of fluid dynamics at Nagoya University in Japan, suggests that helicity dissipates during reconnection. “It’s an open question,” Moffatt said.
Reconnection is central to many turbulent processes, such as feedback between large and small eddies in Earth’s atmosphere, the heating of the solar corona and the generation of Earth’s magnetic field. In thermonuclear fusion — a solar process in which atoms fuse together, releasing massive amounts of energy — a turbulent plasma constantly undergoes reconnection as it relaxes to its minimum energy state. Understanding whether helicity remains constant during this process will help researchers correctly model and replicate fusion in the laboratory. “That’s why it’s an important issue to try to understand,” Moffatt said. “The long-term hope for mankind is to produce energy from fusion.”

Quantities that are “conserved,” or stay constant in time, “give you powerful ways to look at complicated problems,” Irvine explained. “Understanding a new conserved quantity, helicity, could have a huge impact on how we understand flows. It’s one of those holy grails.”

Once the rules of knottedness are established, some scientists say it might be possible to harness them through clever system design to control turbulence. The findings might suggest, for example, a better shape for airplane wings. “Could you braid the turbulence, and would that make it possible for planes to fly closer together?” Kamien asked. “Turbulence appears to be random. But is there some way to keep it from being random?”

Discovery of Quantum Vibrations in 'Microtubules' Corroborates Theory of Consciousness

by Staff Writers Amsterdam, Netherlands (SPX) Jan 21, 2014

The recent discovery of warm temperature quantum vibrations in microtubules inside brain neurons by the research group led by Anirban Bandyopadhyay, PhD, at the National Institute of Material Sciences in Tsukuba, Japan (and now at MIT), corroborates the pair's theory and suggests that EEG rhythms also derive from deeper level microtubule vibrations.

A review and update of a controversial 20-year-old theory of consciousness published in Physics of Life Reviews claims that consciousness derives from deeper level, finer scale activities inside brain neurons. The recent discovery of quantum vibrations in "microtubules" inside brain neurons corroborates this theory, according to review authors Stuart Hameroff and Sir Roger Penrose.
They suggest that EEG rhythms (brain waves) also derive from deeper level microtubule vibrations, and that from a practical standpoint, treating brain microtubule vibrations could benefit a host of mental, neurological, and cognitive conditions.
The theory, called "orchestrated objective reduction" ('Orch OR'), was first put forward in the mid-1990s by eminent mathematical physicist Sir Roger Penrose, FRS, Mathematical Institute and Wadham College, University of Oxford, and prominent anesthesiologist Stuart Hameroff, MD, Anesthesiology, Psychology and Center for Consciousness Studies, The University of Arizona, Tucson. They suggested that quantum vibrational computations in microtubules were "orchestrated" ("Orch") by synaptic inputs and memory stored in microtubules, and terminated by Penrose "objective reduction" ('OR'), hence "Orch OR." Microtubules are major components of the cell structural skeleton.
Orch OR was harshly criticized from its inception, as the brain was considered too "warm, wet, and noisy" for seemingly delicate quantum processes. However, evidence has now shown warm quantum coherence in plant photosynthesis, bird brain navigation, our sense of smell, and brain microtubules.
The recent discovery of warm temperature quantum vibrations in microtubules inside brain neurons by the research group led by Anirban Bandyopadhyay, PhD, at the National Institute of Material Sciences in Tsukuba, Japan (and now at MIT), corroborates the pair's theory and suggests that EEG rhythms also derive from deeper level microtubule vibrations.
In addition, work from the laboratory of Roderick G. Eckenhoff, MD, at the University of Pennsylvania, suggests that anesthesia, which selectively erases consciousness while sparing non-conscious brain activities, acts via microtubules in brain neurons.
"The origin of consciousness reflects our place in the universe, the nature of our existence. Did consciousness evolve from complex computations among brain neurons, as most scientists assert? Or has consciousness, in some sense, been here all along, as spiritual approaches maintain?" ask Hameroff and Penrose in the current review.
"This opens a potential Pandora's Box, but our theory accommodates both these views, suggesting consciousness derives from quantum vibrations in microtubules, protein polymers inside brain neurons, which both govern neuronal and synaptic function, and connect brain processes to self-organizing processes in the fine scale, 'proto-conscious' quantum structure of reality."
After 20 years of skeptical criticism, "the evidence now clearly supports Orch OR," continue Hameroff and Penrose. "Our new paper updates the evidence, clarifies Orch OR quantum bits, or "qubits," as helical pathways in microtubule lattices, rebuts critics, and reviews 20 testable predictions of Orch OR published in 1998 - of these, six are confirmed and none refuted."
An important new facet of the theory is introduced. Microtubule quantum vibrations (e.g. in megahertz) appear to interfere and produce much slower EEG "beat frequencies." Despite a century of clinical use, the underlying origins of EEG rhythms have remained a mystery. Clinical trials of brief brain stimulation aimed at microtubule resonances with megahertz mechanical vibrations using transcranial ultrasound have shown reported improvements in mood, and may prove useful against Alzheimer's disease and brain injury in the future.
Lead author Stuart Hameroff concludes, "Orch OR is the most rigorous, comprehensive and successfully-tested theory of consciousness ever put forth. From a practical standpoint, treating brain microtubule vibrations could benefit a host of mental, neurological, and cognitive conditions."
The review is accompanied by eight commentaries from outside authorities, including an Australian group of Orch OR arch-skeptics. To all, Hameroff and Penrose respond robustly.
Penrose, Hameroff and Bandyopadhyay will explore their theories during a session on "Microtubules and the Big Consciousness Debate" at the Brainstorm Sessions, a public three-day event at the Brakke Grond in Amsterdam, the Netherlands, January 16-18, 2014. They will engage skeptics in a debate on the nature of consciousness, and Bandyopadhyay and his team will couple microtubule vibrations from active neurons to play Indian musical instruments.
"Consciousness depends on anharmonic vibrations of microtubules inside neurons, similar to certain kinds of Indian music, but unlike Western music which is harmonic," Hameroff explains.
"Consciousness in the universe: A review of the 'Orch OR' theory," by Stuart Hameroff, MD, and Roger Penrose, FRS. The review is freely available online on ScienceDirect.
Commentaries on the review are:
"Reply to criticism of the 'Orch OR qubit'-'Orchestrated objective reduction' is scientifically justified," by Stuart Hameroff, MD, and Roger Penrose, FRS;
"Reply to seven commentaries on "Consciousness in the universe: Review of the 'Orch OR' theory," by Stuart Hameroff, MD, and Roger Penrose, FRS.

The Symphony of Life, Revealed - and it is Vibratory

by Staff Writers Buffalo NY (SPX) Jan 21, 2014

Using a new imaging technique they developed, scientists have managed to observe and document the vibrations of lysozyme, an antibacterial protein found in many animals. This graphic visualizes the vibrations in lysozyme as it is excited by terahertz light (depicted by the red wave arrow). Such vibrations, long thought to exist, have never before been described in such detail, said lead researcher Andrea Markelz, a UB physicist. Credit: Credit: Andrea Markelz and Katherine Niessen.

The strings on a violin or the pipes of an organ, the proteins in the human body vibrate in different patterns, scientists have long suspected. Now, a new study provides what researchers say is the first conclusive evidence that this is true.
Using a technique they developed based on terahertz near-field microscopy, scientists from the University at Buffalo and Hauptman-Woodward Medical Research Institute (HWI) have for the first time observed in detail the vibrations of lysozyme, an antibacterial protein found in many animals.
The team found that the vibrations, which were previously thought to dissipate quickly, actually persist in molecules like the "ringing of a bell," said UB physics professor Andrea Markelz, PhD, wh0 led the study.
These tiny motions enable proteins to change shape quickly so they can readily bind to other proteins, a process that is necessary for the body to perform critical biological functions like absorbing oxygen, repairing cells and replicating DNA, Markelz said.
The research opens the door to a whole new way of studying the basic cellular processes that enable life.
"People have been trying to measure these vibrations in proteins for many, many years, since the 1960s," Markelz said. "In the past, to look at these large-scale, correlated motions in proteins was a challenge that required extremely dry and cold environments and expensive facilities."
"Our technique is easier and much faster," she said. "You don't need to cool the proteins to below freezing or use a synchrotron light source or a nuclear reactor - all things people have used previously to try and examine these vibrations."
The findings will appear in Nature Communications on Jan. 16, and publication of information on the research is prohibited until 5 a.m. U.S. Eastern Time on that day.
To observe the protein vibrations, Markelz' team relied on an interesting characteristic of proteins: The fact that they vibrate at the same frequency as the light they absorb.
This is analogous to the way wine glasses tremble and shatter when a singer hits exactly the right note. Markelz explained: Wine glasses vibrate because they are absorbing the energy of sound waves, and the shape of a glass determines what pitches of sound it can absorb. Similarly, proteins with different structures will absorb and vibrate in response to light of different frequencies.
So, to study vibrations in lysozyme, Markelz and her colleagues exposed a sample to light of different frequencies and polarizations, and measured the types of light the protein absorbed.
This technique, developed with Edward Snell, a senior research scientist at HWI and assistant professor of structural biology at UB, allowed the team to identify which sections of the protein vibrated under normal biological conditions. The researchers were also able to see that the vibrations endured over time, challenging existing assumptions.
"If you tap on a bell, it rings for some time, and with a sound that is specific to the bell. This is how the proteins behave," Markelz said. "Many scientists have previously thought a protein is more like a wet sponge than a bell: If you tap on a wet sponge, you don't get any sustained sound."
Markelz said the team's technique for studying vibrations could be used in the future to document how natural and artificial inhibitors stop proteins from performing vital functions by blocking desired vibrations.
"We can now try to understand the actual structural mechanisms behind these biological processes and how they are controlled," Markelz said.
"The cellular system is just amazing," she said. "You can think of a cell as a little machine that does lots of different things - it senses, it makes more of itself, it reads and replicates DNA, and for all of these things to occur, proteins have to vibrate and interact with one another."

Grandma's Experiences Leave a Mark on Your Genes

Your ancestors' lousy childhoods or excellent adventures might change your personality, bequeathing anxiety or resilience by altering the epigenetic expressions of genes in the brain.

By Dan Hurley|Tuesday, June 11, 2013

Alison Mackey/DISCOVER

Darwin and Freud walk into a bar. Two alcoholic mice — a mother and her son — sit on two bar stools, lapping gin from two thimbles.

The mother mouse looks up and says, “Hey, geniuses, tell me how my son got into this sorry state.”

“Bad inheritance,” says Darwin.

“Bad mothering,” says Freud.

For over a hundred years, those two views — nature or nurture, biology or psychology — offered opposing explanations for how behaviors develop and persist, not only within a single individual but across generations.

And then, in 1992, two young scientists following in Freud’s and Darwin’s footsteps actually did walk into a bar. And by the time they walked out, a few beers later, they had begun to forge a revolutionary new synthesis of how life experiences could directly affect your genes — and not only your own life experiences, but those of your mother’s, grandmother’s and beyond.

The bar was in Madrid, where the Cajal Institute, Spain’s oldest academic center for the study of neurobiology, was holding an international meeting. Moshe Szyf, a molecular biologist and geneticist at McGill University in Montreal, had never studied psychology or neurology, but he had been talked into attending by a colleague who thought his work might have some application. Likewise, Michael Meaney, a McGill neurobiologist, had been talked into attending by the same colleague, who thought Meaney’s research into animal models of maternal neglect might benefit from Szyf’s perspective.

Michael Meaney, neurobiologist.

Owen Egan/McGill University

“I can still visualize the place — it was a corner bar that specialized in pizza,” Meaney says. “Moshe, being kosher, was interested in kosher calories. Beer is kosher. Moshe can drink beer anywhere. And I’m Irish. So it was perfect.”

The two engaged in animated conversation about a hot new line of research in genetics. Since the 1970s, researchers had known that the tightly wound spools of DNA inside each cell’s nucleus require something extra to tell them exactly which genes to transcribe, whether for a heart cell, a liver cell or a brain cell. 

One such extra element is the methyl group, a common structural component of organic molecules. The methyl group works like a placeholder in a cookbook, attaching to the DNA within each cell to select only those recipes — er, genes — necessary for that particular cell’s proteins. Because methyl groups are attached to the genes, residing beside but separate from the double-helix DNA code, the field was dubbed epigenetics, from the prefix epi (Greek for over, outer, above).

Originally these epigenetic changes were believed to occur only during fetal development. But pioneering studies showed that molecular bric-a-brac could be added to DNA in adulthood, setting off a cascade of cellular changes resulting in cancer. Sometimes methyl groups attached to DNA thanks to changes in diet; other times, exposure to certain chemicals appeared to be the cause. Szyf showed that correcting epigenetic changes with drugs could cure certain cancers in animals. 

Geneticists were especially surprised to find that epigenetic change could be passed down from parent to child, one generation after the next. A study from Randy Jirtle of Duke University showed that when female mice are fed a diet rich in methyl groups, the fur pigment of subsequent offspring is permanently altered. Without any change to DNA at all, methyl groups could be added or subtracted, and the changes were inherited much like a mutation in a gene.

Moshe Szyf, molecular biologist and geneticist.

McGill University

Now, at the bar in Madrid, Szyf and Meaney considered a hypothesis as improbable as it was profound: If diet and chemicals can cause epigenetic changes, could certain experiences — child neglect, drug abuse or other severe stresses — also set off epigenetic changes to the DNA inside the neurons of a person’s brain? That question turned out to be the basis of a new field, behavioral epigenetics, now so vibrant it has spawned dozens of studies and suggested profound new treatments to heal the brain.

According to the new insights of behavioral epigenetics, traumatic experiences in our past, or in our recent ancestors’ past, leave molecular scars adhering to our DNA. Jews whose great-grandparents were chased from their Russian shtetls; Chinese whose grandparents lived through the ravages of the Cultural Revolution; young immigrants from Africa whose parents survived massacres; adults of every ethnicity who grew up with alcoholic or abusive parents — all carry with them more than just memories. 

Like silt deposited on the cogs of a finely tuned machine after the seawater of a tsunami recedes, our experiences, and those of our forebears, are never gone, even if they have been forgotten. They become a part of us, a molecular residue holding fast to our genetic scaffolding. The DNA remains the same, but psychological and behavioral tendencies are inherited. You might have inherited not just your grandmother’s knobby knees, but also her predisposition toward depression caused by the neglect she suffered as a newborn. 

Or not. If your grandmother was adopted by nurturing parents, you might be enjoying the boost she received thanks to their love and support. The mechanisms of behavioral epigenetics underlie not only deficits and weaknesses but strengths and resiliencies, too. And for those unlucky enough to descend from miserable or withholding grandparents, emerging drug treatments could reset not just mood, but the epigenetic changes themselves. Like grandmother’s vintage dress, you could wear it or have it altered. The genome has long been known as the blueprint of life, but the epigenome is life’s Etch A Sketch: Shake it hard enough, and you can wipe clean the family curse.

Voodoo Genetics 

Twenty years after helping to set off a revolution, Meaney sits behind a wide walnut table that serves as his desk. A January storm has deposited half a foot of snow outside the picture windows lining his fourth-floor corner office at the Douglas Institute, a mental health affiliate of McGill. He has the rugged good looks and tousled salt-and-pepper hair of someone found on a ski slope — precisely where he plans to go this weekend. On the floor lays an arrangement of helium balloons in various stages of deflation. “Happy 60th!” one announces. 

“I’ve always been interested in what makes people different from each other,” he says. “The way we act, the way we behave — some people are optimistic, some are pessimistic. What produces that variation? Evolution selects the variance that is most successful, but what produces the grist for the mill?” 

Meaney pursued the question of individual differences by studying how the rearing habits of mother rats caused lifelong changes in their offspring. Research dating back to the 1950s had shown that rats handled by humans for as little as five to 15 minutes per day during their first three weeks of life grew up to be calmer and less reactive to stressful environments compared with their non-handled littermates. Seeking to tease out the mechanism behind such an enduring effect, Meaney and others established that the benefit was not actually conveyed by the human handling. Rather, the handling simply provoked the rats’ mothers to lick and groom their pups more, and to engage more often in a behavior called arched-back nursing, in which the mother gives the pups extra room to suckle against her underside.

“It’s all about the tactile stimulation,” Meaney says.

In a landmark 1997 paper in Science, he showed that natural variations in the amount of licking and grooming received during infancy had a direct effect on how stress hormones, including corticosterone, were expressed in adulthood. The more licking as babies, the lower the stress hormones as grown-ups. It was almost as if the mother rats were licking away at a genetic dimmer switch. What the paper didn’t explain was how such a thing could be possible. 

"What we had done up to that point in time was to identify maternal care and its influence on specific genes,” Meaney says. “But epigenetics wasn’t a topic I knew very much about.”

And then he met Szyf.

Alison Mackey/DISCOVER

Postnatal Inheritance 

“I was going to be a dentist,” Szyf says with a laugh. Slight, pale and balding, he sits in a small office at the back of his bustling laboratory — a room so Spartan, it contains just a single picture, a photograph of two embryos in a womb.

Needing to write a thesis in the late 1970s for his doctorate in dentistry at Hebrew University of Jerusalem, Szyf approached a young biochemistry professor named Aharon Razin, who had recently made a splash by publishing his first few studies in some of the world’s top scientific journals. The studies were the first to show that the action of genes could be modulated by structures called methyl groups, a subject about which Szyf knew precisely nothing. But he needed a thesis adviser, and Razin was there. Szyf found himself swept up to the forefront of the hot new field of epigenetics and never looked back.

Until researchers like Razin came along, the basic story line on how genes get transcribed in a cell was neat and simple. DNA is the master code, residing inside the nucleus of every cell; RNA transcribes the code to build whatever proteins the cell needs. Then some of Razin’s colleagues showed that methyl groups could attach to cytosine, one of the chemical bases in DNA and RNA. 

It was Razin, working with fellow biochemist Howard Cedar, who showed these attachments weren’t just brief, meaningless affairs. The methyl groups could become married permanently to the DNA, getting replicated right along with it through a hundred generations. As in any good marriage, moreover, the attachment of the methyl groups significantly altered the behavior of whichever gene they wed, inhibiting its transcription, much like a jealous spouse. It did so, Razin and Cedar showed, by tightening the thread of DNA as it wrapped around a molecular spool, called a histone, inside the nucleus. The tighter it is wrapped, the harder to produce proteins from the gene. 

Consider what that means: Without a mutation to the DNA code itself, the attached methyl groups cause long-term, heritable change in gene function. Other molecules, called acetyl groups, were found to play the opposite role, unwinding DNA around the histone spool, and so making it easier for RNA to transcribe a given gene.

By the time Szyf arrived at McGill in the late 1980s, he had become an expert in the mechanics of epigenetic change. But until meeting Meaney, he had never heard anyone suggest that such changes could occur in the brain, simply due to maternal care.

“It sounded like voodoo at first,” Szyf admits. “For a molecular biologist, anything that didn’t have a clear molecular pathway was not serious science. But the longer we talked, the more I realized that maternal care just might be capable of causing changes in DNA methylation, as crazy as that sounded. So Michael and I decided we’d have to do the experiment to find out.”

Thinkstock

Actually, they ended up doing a series of elaborate experiments. With the assistance of postdoctoral researchers, they began by selecting mother rats who were either highly attentive or highly inattentive. Once a pup had grown up into adulthood, the team examined its hippocampus, a brain region essential for regulating the stress response. In the pups of inattentive mothers, they found that genes regulating the production of glucocorticoid receptors, which regulate sensitivity to stress hormones, were highly methylated; in the pups of conscientious moms, the genes for the glucocorticoid receptors were rarely methylated.

Methylation just gums up the works. So the less the better when it comes to transcribing the affected gene. In this case, methylation associated with miserable mothering prevented the normal number of glucocorticoid receptors from being transcribed in the baby’s hippocampus. And so for want of sufficient glucocorticoid receptors, the rats grew up to be nervous wrecks.

To demonstrate that the effects were purely due to the mother’s behavior and not her genes, Meaney and colleagues performed a second experiment. They took rat pups born to inattentive mothers and gave them to attentive ones, and vice versa. As they predicted, the rats born to attentive mothers but raised by inattentive ones grew up to have low levels of glucocorticoid receptors in their hippocampus and behaved skittishly. Likewise, those born to bad mothers but raised by good ones grew up to be calm and brave and had high levels of glucocorticoid receptors.

Before publishing their findings, Meaney and Szyf conducted a third crucial experiment, hoping to overwhelm the inevitable skeptics who would rise up to question their results. After all, it could be argued, what if the epigenetic changes observed in the rats’ brains were not directly causing the behavioral changes in the adults, but were merely co-occurring? Freud certainly knew the enduring power of bad mothers to screw up people’s lives. Maybe the emotional effects were unrelated to the epigenetic change.

To test that possibility, Meaney and Szyf took yet another litter of rats raised by rotten mothers. This time, after the usual damage had been done, they infused their brains with trichostatin A, a drug that can remove methyl groups. These animals showed none of the behavioral deficits usually seen in such offspring, and their brains showed none of the epigenetic changes.

“It was crazy to think that injecting it straight into the brain would work,” says Szyf. “But it did. It was like rebooting a computer.”

Jay Smith/DISCOVER

Despite such seemingly overwhelming evidence, when the pair wrote it all up in a paper, one of the reviewers at a top science journal refused to believe it, stating he had never before seen evidence that a mother’s behavior could cause epigenetic change.

“Of course he hadn’t,” Szyf says. “We wouldn’t have bothered to report the study if it had already been proved.”

In the end, their landmark paper, “Epigenetic programming by maternal behavior,” was published in June 2004 in the journal Nature Neuroscience.

Meaney and Szyf had proved something incredible. Call it postnatal inheritance: With no changes to their genetic code, the baby rats nonetheless gained genetic attachments due solely to their upbringing — epigenetic additions of methyl groups sticking like umbrellas out the elevator doors of their histones, gumming up the works and altering the function of the brain.

The Beat Goes On

Together, Meaney and Szyf have gone on to publish some two-dozen papers, finding evidence along the way of epigenetic changes to many other genes active in the brain. Perhaps most significantly, in a study led by Frances Champagne — then a graduate student in Meaney’s lab, now an associate professor with her own lab at Columbia University in New York — they found that inattentive mothering in rodents causes methylation of the genes for estrogen receptors in the brain. When those babies grow up, the resulting decrease of estrogen receptors makes them less attentive to their babies. And so the beat goes on. 

As animal experiments continue apace, Szyf and Meaney have entered into the next great step in the study of behavioral epigenetics: human studies. In a 2008 paper, they compared the brains of people who had committed suicide with the brains of people who had died suddenly of factors other than suicide. They found excess methylation of genes in the suicide brains’ hippocampus, a region critical to memory acquisition and stress response. If the suicide victims had been abused as children, they found, their brains were more methylated.

Alison Mackey/DISCOVER

Why can’t your friend “just get over” her upbringing by an angry, distant mother? Why can’t she “just snap out of it”? The reason may well be due to methyl groups that were added in childhood to genes in her brain, thereby handcuffing her mood to feelings of fear and despair. 

Of course, it is generally not possible to sample the brains of living people. But examining blood samples in humans is routine, and Szyf has gone searching there for markers of epigenetic methylation. Sure enough, in 2011 he reported on a genome-wide analysis of blood samples taken from 40 men who participated in a British study of people born in England in 1958. 

All the men had been at a socioeconomic extreme, either very rich or very poor, at some point in their lives ranging from early childhood to mid-adulthood. In all, Szyf analyzed the methylation state of about 20,000 genes. Of these, 6,176 genes varied significantly based on poverty or wealth. Most striking, however, was the finding that genes were more than twice as likely to show methylation changes based on family income during early childhood versus economic status as adults.

Timing, in other words, matters. Your parents winning the lottery or going bankrupt when you’re 2 years old will likely affect the epigenome of your brain, and your resulting emotional tendencies, far more strongly than whatever fortune finds you in middle age. 

Last year, Szyf and researchers from Yale University published another study of human blood samples, comparing 14 children raised in Russian orphanages with 14 other Russian children raised by their biological parents. They found far more methylation in the orphans’ genes, including many that play an important role in neural communication and brain development and function. 

“Our study shows that the early stress of separation from a biological parent impacts long-term programming of genome function; this might explain why adopted children may be particularly vulnerable to harsh parenting in terms of their physical and mental health,” said Szyf’s co-author, psychologist Elena Grigorenko of the Child Study Center at Yale. “Parenting adopted children might require much more nurturing care to reverse these changes in genome regulation.”

A case study in the epigenetic effects of upbringing in humans can be seen in the life of Szyf’s and Meaney’s onetime collaborator, Frances Champagne. “My mom studied prolactin, a hormone involved in maternal behavior. She was a driving force in encouraging me to go into science,” she recalls. Now a leading figure in the study of maternal influence, Champagne just had her first child, a daughter. And epigenetic research has taught her something not found in the What to Expect books or even her mother’s former lab. 

“The thing I’ve gained from the work I do is that stress is a big suppressor of maternal behavior,” she says. “We see it in the animal studies, and it’s true in humans. So the best thing you can do is not to worry all the time about whether you’re doing the right thing. Keeping the stress level down is the most important thing. And tactile interaction — that’s certainly what the good mother rats are doing with their babies. That sensory input, the touching, is so important for the developing brain.” 

The Mark Of Cain 

The message that a mother’s love can make all the difference in a child’s life is nothing new. But the ability of epigenetic change to persist across generations remains the subject of debate. Is methylation transmitted directly through the fertilized egg, or is each infant born pure, a methylated virgin, with the attachments of methyl groups slathered on solely by parents after birth? 

Neuroscientist Eric Nestler of the Icahn School of Medicine at Mount Sinai in New York has been seeking an answer for years. In one study, he exposed male mice to 10 days of bullying by larger, more aggressive mice. At the end of the experiment, the bullied mice were socially withdrawn. 

To test whether such effects could be transmitted to the next generation, Nestler took another group of bullied mice and bred them with females, but kept them from ever meeting their offspring. 

Alison Mackey/DISCOVER

Despite having no contact with their depressed fathers, the offspring grew up to be hypersensitive to stress. “It was not a subtle effect; the offspring were dramatically more susceptible to developing signs of depression,” he says.

In further testing, Nestler took sperm from defeated males and impregnated females through in vitro fertilization. The offspring did not show most of the behavioral abnormalities, suggesting that epigenetic transmission may not be at the root. Instead, Nestler proposes, “the female might know she had sex with a loser. She knows it’s a tainted male she had sex with, so she cares for her pups differently,” accounting for the results.

Despite his findings, no consensus has yet emerged. The latest evidence, published in the Jan. 25 issue of the journal Science, suggests that epigenetic changes in mice are usually erased, but not always. The erasure is imperfect, and sometimes the affected genes may make it through to the next generation, setting the stage for transmission of the altered traits in descendants as well. 

What’s Next?

The studies keep piling on. One line of research traces memory loss in old age to epigenetic alterations in brain neurons. Another connects post-traumatic stress disorder to methylation of the gene coding for neurotrophic factor, a protein that regulates the growth of neurons in the brain.

If it is true that epigenetic changes to genes active in certain regions of the brain underlie our emotional and intellectual intelligence — our tendency to be calm or fearful, our ability to learn or to forget — then the question arises: Why can’t we just take a drug to rinse away the unwanted methyl groups like a bar of epigenetic Irish Spring? 

The hunt is on. Giant pharmaceutical and smaller biotech firms are searching for epigenetic compounds to boost learning and memory. It has been lost on no one that epigenetic medications might succeed in treating depression, anxiety and post-traumatic stress disorder where today’s psychiatric drugs have failed. 

But it is going to be a leap. How could we be sure that epigenetic drugs would scrub clean only the dangerous marks, leaving beneficial — perhaps essential — methyl groups intact? And what if we could create a pill potent enough to wipe clean the epigenetic slate of all that history wrote? If such a pill could free the genes within your brain of the epigenetic detritus left by all the wars, the rapes, the abandonments and cheated childhoods of your ancestors, would you take it?