Fool’s gold gives scientists priceless insight into Earth’s evolution

Posted by Biomechanism 

(“Biomechanism.com“) — Fool’s gold is providing scientists with valuable insights into a turning point in the Earth’s evolution, which took place billions of years ago.

Scientists are recreating ancient forms of the mineral pyrite – dubbed fool’s gold for its metallic lustre – that reveal details of past geological events.

Pyrite is a shiny yellow mineral which is often called "fool’s gold" because many prospectors were fooled into thinking they had found gold. Pyrite gets its name from the Greek word for fire, because it can give off sparks when it is struck. It has been used to light fires for thousands of years. Pyrite is commercially used for the production of sulphur dioxide and in the manufacture of sulphuric acid.

Detailed analysis of the mineral is giving fresh insight into the Earth before the Great Oxygenation Event, which took place 2.4 billion years ago. This was a time when oxygen released by early forms of bacteria gave rise to new forms of plant and animal life, transforming the Earth’s oceans and atmosphere.

Studying the composition of pyrite enables a geological snapshot of events at the time when it was formed. Studying the composition of different forms of iron in fool’s gold gives scientists clues as to how conditions such as atmospheric oxygen influenced the processes forming the compound.

The latest research shows that bacteria – which would have been an abundant life form at the time – did not influence the early composition of pyrite. This result, which contrasts with previous thinking, gives scientists a much clearer picture of the process.

More extensively, their discovery enables better understanding of geological conditions at the time, which informs how the oceans and atmosphere evolved.

The research, funded by the Natural Environment Research Council and the Edinburgh Collaborative of Subsurface Science and Engineering, was published in Science.

Dr Ian Butler, who led the research, said: “Technology allows us to trace scientific processes that we can’t see from examining the mineral composition alone, to understand how compounds were formed. This new information about pyrite gives us a much sharper tool with which to analyse the early evolution of the Earth, telling us more about how our planet was formed.”

Dr Romain Guilbaud, investigator on the study, said: “Our discovery enables a better understanding of how information on the Earth’s evolution, recorded in ancient minerals, can be interpreted.”

Harvard bioengineers identify the cellular mechanisms of traumatic brain injury

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Findings offer new hope for treatment of TBI in veterans wounded by explosions.

(“Biomechanism.com“) — Bioengineers at Harvard have identified, for the very first time, the mechanism for diffuse axonal injury and explained why cerebral vasospasm is more common in blast-induced brain injuries than in brain injuries typically suffered by civilians.

The research addresses two major aspects of traumatic brain injury (TBI), with significant implications for the medical treatment of soldiers wounded by explosions.

Caption: Left: A healthy neuron, with its dendrites and axon intact. Right: The damaged neuron has retracted its arms, breaking essential connections with its neighbors. Credit: Photo courtesy of Matthew Hemphill, Borna Dabiri, and Sylvain Gabriele.

Two papers, published in the journals Proceedings of the National Academy of Sciences (PNAS) and PLoS One, provide the most comprehensive explanation to date of how mechanical forces can be translated into subtly disastrous physiological changes within the brain’s neurons and vasculature.

“These results have been a long time coming,” says principal investigator Kevin Kit Parker, a Professor of Bioengineering at Harvard’s School of Engineering and Applied Sciences (SEAS) and a major in the U.S. Army. “So many young men and women are returning from military service with brain injuries, and we just don’t know how to help them.”

When the brain encounters a jarring force, such as an exploding roadside bomb, the delicate tissue slams against the skull. The result, if the patient survives, can be a temporary concussion, a more dangerous hemorrhage, or long-term TBI, which can even lead to the early onset of Parkinson’s or Alzheimer’s diseases.

Inspired by Parker’s own military experience, the Disease Biophysics Group (based at SEAS and at the Wyss Institute for Biologically Inspired Engineering at Harvard) has taken up the cause. Using cutting-edge tissue engineering techniques—essentially creating a living brain on a chip—biologists, physicists, engineers, and materials scientists collaborate to study brain injury and potential targets for treatment.

Now, researchers in his group have identified the cellular mechanism that initiates diffuse axonal injury, offering urgently needed direction for research in therapeutic treatments.

Their studies show that integrins, receptor proteins embedded in the cell membrane, provide the crucial link between external forces and internal physiological changes.

Integrins connect the structural components within the cell (such as actin and other cytoskeletal proteins) with the extracellular matrix that binds cells together into tissue. Collectively, this network of structural and signaling components is referred to as the focal adhesion complex.

Parker’s research has demonstrated that the forces unleashed by an explosion physically disrupt the structure of the focal adhesion complex, setting off a chain reaction of destructive molecular signals within the nerve cells of the brain.

Inside the neuron, integrins normally mediate the activation of the proteins RhoA and Rho kinase (ROCK). When the focal adhesion complex is disturbed, the Rho-ROCK signaling pathway goes haywire: it directs the motor protein actin to retract the cell’s arm-like axons, disconnecting the neurons from each other and collapsing the cellular networks that constitute the brain.

Caption: Bioengineers at Harvard have identified the mechanism for diffuse axonal injury and explained why cerebral vasospasm is common after an IED explosion. (NOTE: PI Kit Parker is NOT in this photo.) Photo: U.S. Department of Defense.

“Our research has shown that abrupt mechanical forces, such as those from a blast wave and transduced by integrins, can result in neural injury,” says Matthew A. Hemphill, who with Borna Dabiri (S.B. ’07) and Sylvain Gabriele, is a lead author of the paper in PLoS One. Dabiri and Hemphill are currently graduate students at SEAS, and Gabriele is a former postdoctoral fellow in Parker’s lab.

Adds Dabiri: “Encouragingly, we also found that treating the neural tissue with HA-1077, which is a ROCK inhibitor, within the first 10 minutes of injury, reduced the number of focal swellings. We think that further study of ROCK inhibition could lead to viable treatments within the near future.”

A second direction of research in Parker’s lab has solved another mystery in TBI, explaining why cerebral vasospasm, a dangerous remodeling of the brain’s blood vessels, occurs more commonly in TBI caused by explosions than in other types of brain trauma.

“Until now, other researchers looking at TBI focused on ion channels and membrane poration, and it was generally accepted that cerebralvasospasm was only caused by hemorrhaging. It turns out that it’s much morecomplicated than that,” says Patrick W. Alford, a former postdoctoral fellow in Parker’s lab and lead author of the paper inPNAS. “Integrins and Rho-ROCK signaling appear to be players in both diffuse axonal injury and cerebral vasospasm.”

As reported in PNAS, the forces exerted on arteries are different during an explosive blast than during blunt force trauma. Subarachnoid hemorrhage, which can occur in very severe head injuries, is known to cause vasospasm, but Parker’s new research shows that the unique force of an explosion can also cause vasospasm by itself.

The blast from an explosion creates a surge in blood pressure, which stretches the walls of the blood vessels in the brain. To study this, Parker’s team of bioengineers built artificial arteries, made of living vascular cells, and used a specialized machine to rapidly stretch them, simulating an explosion. While this stretching did not overtly damage the cellular structure, it did cause an immediate hypersensitivity to the protein endothelin-1.

Endothelin-1 is known to stimulate vascular cells to absorb calcium ions, which affect actin—the same protein involved in the retraction of axons.

In the 24 hours following the simulated blast, the vascular tissues hypercontract and undergo a complete phenotypic switch, disrupting the overall function of the tissue. Both of these behaviors are characteristic of cerebral vasospasm.

Most importantly, as in the neural tissue, the Rho-ROCK signaling pathway plays an important role in the behavior of actin and the cells’ contraction. Parker’s team found that inhibition of Rho soon after the injury can mitigate the harmful effects of the blast on the brain’s vascular system.

“We have established a toe-hold as we try to climb up on top of this problem,” says Parker. “In many ways, this work is just the beginning.”

_______________________

Parker’s coauthors on the paper in PLoS One are Hemphill, currently at the University of Mons in Belgium; Dabiri, who beganworking in Parker’s lab as an undergraduate; Gabriele, who is now at the University of Mons; Lucas Kerscher, a visiting student; Christian Franck, formerly a postdoctoral fellow at SEAS and now at Brown University; Josue A. Goss, a staff engineer at SEAS; and Alford, who is now at the University ofMinnesota.

Parker’s coauthors on the paper in PNAS are Alford; Dabiri; Goss; Hemphill; and Mark D. Brigham, a graduate student at SEAS.

The Disease Biophysics Group received financial support from the Defense Advanced Research Projects Agency (DARPA) Preventing Violent Explosive Neurologic Trauma (PREVENT) Program, the Department of Defense, and the Harvard School of Engineering and Applied Sciences (SEAS).

The researchers also gratefully acknowledge the use of facilities at the Harvard Center for Nanoscale Systems, a member of the National Nanotechnology Infrastructure Network (NNIN), which is funded by the National Science Foundation (NSF).

Life scientists use novel technique to produce genetic map for African Americans

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UCLA life scientists and colleagues have produced one of the first high-resolution genetic maps for African American populations. A genetic map reveals the precise locations across the genome where DNA from a person’s father and mother have been stitched together through a biological process called “recombination.” This process results in new genetic combinations that are then passed on to the person’s children.

The mixture of African and European ancestry typical in the DNA of African Americans is reflected in recombination rates. Photo: MIKE BROWN/Landov.

The new map will help disease geneticists working to map genetic diseases in African Americans because it provides a more accurate understanding of recombination rates among that population, said the senior author of the research, John Novembre, a UCLA assistant professor of ecology and evolutionary biology and of bioinformatics. The map could help scientists learn the roots of these diseases and discover genes that play a key role in them.

The study was published July 20 in the online version of the journal Nature Genetics and will be published in the print edition at a later date.

“Research aimed at finding disease variants will be improved by this tool, which could lead to better medications to help ameliorate the effects of those disease variants,” Novembre said. “Health researchers can use a recombination map to refine where a disease gene might be.”

Prior to this research, which was conducted by scientists from seven institutions, recombination had mainly been studied in European populations.

“Now we have a map for African Americans that researchers can use as a tool, instead of using a European map or an African map,” said Novembre, a member of UCLA’s Interdepartmental Program in Bioinformatics.

A second, independent study, led by David Reich at Harvard University and Simon Myers at Oxford University, used a similar approach to infer an African American recombination map. That research was published this week in Nature.

“While recombination rates between populations are very similar when you look at the broadest scales of the genome, we start to see variation in recombination between populations when we zoom in,” said Daniel Wegmann, a UCLA postdoctoral scholar in Novembre’s laboratory and the lead author of the study. “There are clear differences in recombination between Africans and Europeans, and African Americans tend to have a map that is a mixture between the African and European map, reflecting the mixture that took place between these two groups.

“If the position of a mutation is unknown and you want to pinpoint a gene linked to a disease, then recombination is important to help reveal in what region the gene lies,” Wegmann said.

The mixture of African and European ancestry typical in the DNA of African Americans is reflected in recombination rates, Novembre said.

“No high-resolution recombination map has been inferred before for populations where the individuals have ancestry from different parts of the globe,” Novembre said. “African Americans represent a unique combination of African and European ancestry. We found that if you know an African recombination rate for one region of the genome and you know the European rate, the African American rate sits about 80 percent of the way between the two. That is interesting, because the ancestry of African American DNA, on average, is 80 percent from African ancestral sources and 20 percent from European ancestral sources. The recombination rate reflects the ancestry.”

The life scientists used an innovative method involving population genetic models in which they scanned the individual genomes of 2,565 African Americans, as well as 299 African Caribbeans, to study where in the genome each had African ancestry, where they had European ancestry, and where the “switch points” were that mark the location where the ancestry of a DNA segment changes.

Novembre and colleagues studied the ancestry of DNA segments to reconstruct where recombinations have occurred.

“The key is to uncover the ancestry of each segment of the genome,” Novembre said. “Switch points enable us to identify recombination ‘hot spots,’ where recombination rates are high.”

Explaining recombination, Novembre said, “When we pass on DNA to our children, we stitch together the DNA we received from our mother and father. The resulting DNA alternates between DNA from your mother and from your father, and the recombination points are the boundaries. Those points could be chosen uniformly across the whole chromosome, but studies have found that recombinations occur in some locations in the chromosome more than in others. Locations in the chromosome have particular recombination rates — the rate at which break points occur in that location.

“It is difficult to identify, by studying chromosomes directly, where the stitch points are between maternal and paternal DNA,” he said. “In individuals of mixed ancestry, however, such as African Americans and African Caribbeans, we can identify switch points between African ancestry and European ancestry. These switch points mark locations where recombinations have occurred at some point in the past.”

“There are regions of our map that differ from what we would expect,” Wegmann said. “We see locations where there are deficiencies in recombination, and they line up with the locations of mutations that rearrange the genome and flip a piece of DNA to invert it. When you have a normal copy of the DNA and an inverted copy of the DNA, one from your mother and one from your father, this inversion suppresses recombination.”

Of some 3 billion base pairs in a person’s genome, the scientists were able to resolve recombination rates down to 50,000 base pairs of the DNA — an impressive figure.

Comparing this African American recombination map with that of other populations enables researchers to locate recombination hot spots, which have highly elevated rates of recombination.

In addition to the applications for disease mapping, the research provides broad insights into the fundamental biological process of recombination.

“We want to learn how recombination rates vary across the genome,” Novembre said.

Epigenetic ‘memory’ key to nature versus nurture

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(“Biomechanism.com“) — Researchers funded by the Biotechnology and Biological Sciences Research Council (BBSRC) at the John Innes Centre have made a discovery, reported this evening (24 July) in Nature, that explains how an organism can create a biological memory of some variable condition, such as quality of nutrition or temperature. The discovery explains the mechanism of this memory – a sort of biological switch – and how it can also be inherited by offspring.

Epigenetic cellular memory

The work was led by Professor Martin Howard and Professor Caroline Dean at the John Innes Centre, which receives strategic funding from BBSRC. Funding for the project came from BBSRC, the European Research Council, and The Royal Society.

Professor Dean said “There are quite a few examples that we now know of where the activity of genes can be affected in the long term by environmental factors. And in some cases the environment of an individual can actually affect the biology or physiology of their offspring but there is no change to the genome sequence.”

For example, some studies have shown that in families where there was a severe food shortage in the grandparents’ generation, the children and grandchildren have a greater risk of cardiovascular disease and diabetes, which could be explained by epigenetic memory. But until now there hasn’t been a clear mechanism to explain how individuals could develop a “memory” of a variable factor, such as nutrition.

The team used the example of how plants “remember” the length of the cold winter period in order to exquisitely time flowering so that pollination, development, seed dispersal and germination can all happen at the appropriate time.

Professor Howard said “We already knew quite a lot about the genes involved in flowering and it was clear that something goes on in winter that affects the timing of flowering, according to the length of the cold period.”

Using a combination of mathematical modelling and experimental analysis the team has uncovered the system by which a key gene called FLC is either completely off or completely on in any one cell and also later in its progeny. They found that the longer the cold period, the higher the proportion of cells that have FLC stably flipped to the off position. This delays flowering and is down to a phenomenon known as epigenetic memory.

Epigenetic memory comes in various guises, but one important form involves histones – the proteins around which DNA is wrapped. Particular chemical modifications can be attached to histones and these modifications can then affect the expression of nearby genes, turning them on or off. These modifications can be inherited by daughter cells, when the cells divide, and if they occur in the cells that form gametes (e.g. sperm in mammals or pollen in plants) then they can also pass on to offspring.

Together with Dr Andrew Angel (also at the John Innes Centre), Professor Howard produced a mathematical model of the FLC system. The model predicted that inside each individual cell, the FLC gene should be either completely activated or completely silenced, with the fraction of cells switching to the silenced state increasing with longer periods of cold.

To provide experimental evidence to back up the model, Dr Jie Song in Prof. Dean’s group used a technique where any cell that had the FLC gene switched on, showed up blue under a microscope. From her observations, it was clear that cells were either completely switched or not switched at all, in agreement with the theory.

Dr Song also showed that the histone proteins near the FLC gene were modified during the cold period, in such a way that would account for the switching off of the gene.

Professor Douglas Kell, Chief Executive, BBSRC said “This work not only gives us insight into a phenomenon that is crucial for future food security – the timing of flowering according to climate variation – but it uncovers an important biomechanism that is at play right across biology. This is a great example of where the research that BBSRC funds can provide not only a focus on real life problems, but also a grounding in the fundamental tenets of biology that will underpin the future of the field. It also demonstrates the value of multidisciplinary working at the interface between biology, physics and mathematics.”