Category Archives: Research

How Cells Age

A new study by Harvard Medical School researchers reveals that the biochemical mechanism that makes yeast grow old has a surprising parallel in mice, suggesting it may be a universal cause of aging in all organisms.
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In young organisms, SIRT1 effectively doubles as a gene-expression regulator and a DNA repairer. But when DNA damage accumulates—as it does with age—SIRT1 becomes too busy fixing broken DNA to keep the expression of hundreds of genes in check. This process is so similar to what happens in aging yeast that its discoverers believe it may represent a universal mechanism of aging.

Harvard researchers gain new insight into aging

Aging may be a case of neglect — an absentee landlord at the cellular level that allows gene activity to go awry, according to a study published today.

Scientists have long known that aging causes gene expression to change, and DNA damage to accumulate. But now, research led by Harvard Medical School scientists explains the connection between the two processes in mammals.

The paper, published in the journal Cell, found that a multi-tasking protein called SIRT1 that normally acts as guardian of the genome gets dragged away to DNA fix-it jobs. When the protein abandons its normal post to work as a genetic handyman, order unravels elsewhere in the cell. Genes that are normally under its careful watch begin to flip on.

“What this paper actually implies is that aspects of aging may be reversible,” said David Sinclair, a Harvard Medical School biologist who led the research. “It sounds crazy, but in principle it should be possible to restore the youthful set of genes, the patterns that are on and off.”

The study is just the latest to draw yet more attention to sirtuins, proteins involved in the aging process

Aging is fascinating. By and large people just accept it. We see it happen to those all around us, without exception. But what causes biological aging? It is an interesting area of research.

Rate of Cancer Detected and Death Rates Declines

Declines in Cancer Incidence and Death Rates in report from the National Cancer Institute and CDC:

“The drop in incidence seen in this year’s Annual Report is something we’ve been waiting to see for a long time,” said Otis W. Brawley, M.D., chief medical officer of the American Cancer Society (ACS). “However, we have to be somewhat cautious about how we interpret it, because changes in incidence can be caused not only by reductions in risk factors for cancer, but also by changes in screening practices. Regardless, the continuing drop in mortality is evidence once again of real progress made against cancer, reflecting real gains in prevention, early detection, and treatment.”
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According to a U.S. Surgeon General’s report, cigarette smoking accounts for approximately 30 percent of all cancer deaths, with lung cancer accounting for 80 percent of the smoking-attributable cancer deaths. Other cancers caused by smoking include cancers of the oral cavity, pharynx, larynx, esophagus, stomach, bladder, pancreas, liver, kidney, and uterine cervix and myeloid leukemia.

Diagnoses Of Cancer Decline

The analysis found that the overall incidence of cancer began inching down in 1999, but not until the data for 2005 were analyzed was it clear that a long-term decline was underway. “The take-home message is that many of the things we’ve been telling people to do to be healthy have finally reached the point where we can say that they are working,” Brawley said. “These things are really starting to pay off.”

Brawley and others cautioned, however, that part of the reduction could be the result of fewer people getting screened for prostate and breast cancers. In addition, the rates at which many other types of cancer are being diagnosed are still increasing
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Some experts said the drop was not surprising, noting that it was primarily the result of a fall in lung cancer because of declines in smoking that occurred decades ago. They criticized the ongoing focus on detecting and treating cancer and called for more focus on prevention.

“The whole cancer establishment has been focused on treatment, which has not been terribly productive,” said John C. Bailar III, who studies cancer trends at the National Academy of Sciences. “I think what people should conclude from this is we ought to be putting most of our resources where we know there has been progress, almost in spite of what we’ve done, and stop this single-minded focus on treatment.”

Rat Brain Cells, in a Dish, Flying a Plane

Adaptive Flight Control With Living Neuronal Networks on Microelectrode Arrays (open access paper) by Thomas B. DeMarse and Karl P. Dockendorf Department of Biomedical Engineering, University of Florida

investigating the ability of living neurons to act as a set of neuronal weights which were used to control the flight of a simulated aircraft. These weights were manipulated via high frequency stimulation inputs to produce a system in which a living neuronal network would “learn” to control an aircraft for straight and level flight.

A system was created in which a network of living rat cortical neurons were slowly adapted to control an aircraft’s flight trajectory. This was accomplished by using high frequency stimulation pulses delivered to two independent channels, one for pitch, and one for roll. This relatively simple system was able to control the pitch and roll of a simulated aircraft.

When Dr. Thomas DeMarse first puts the neurons in the dish, they look like little more than grains of sand sprinkled in water. However, individual neurons soon begin to extend microscopic lines toward each other, making connections that represent neural processes. “You see one extend a process, pull it back, extend it out — and it may do that a couple of times, just sampling who’s next to it, until over time the connectivity starts to establish itself,” he said. “(The brain is) getting its network to the point where it’s a live computation device.”

To control the simulated aircraft, the neurons first receive information from the computer about flight conditions: whether the plane is flying straight and level or is tilted to the left or to the right. The neurons then analyze the data and respond by sending signals to the plane’s controls. Those signals alter the flight path and new information is sent to the neurons, creating a feedback system.

“Initially when we hook up this brain to a flight simulator, it doesn’t know how to control the aircraft,” DeMarse said. “So you hook it up and the aircraft simply drifts randomly. And as the data come in, it slowly modifies the (neural) network so over time, the network gradually learns to fly the aircraft.”

Although the brain currently is able to control the pitch and roll of the simulated aircraft in weather conditions ranging from blue skies to stormy, hurricane-force winds, the underlying goal is a more fundamental understanding of how neurons interact as a network, DeMarse said.

Broken Window Theory Bolstered with Experiments

The broken window theory is that as the visible deterioration of an area (broken windows, graffiti, lettering…) takes place, crime will increase. And that this starts a cycle of decline for the area feeds upon itself (a negatively reinforcing loop in system thinking parlance). The theory was put forth in an article in The Atlantic in 1982 by George L. Kelling and James Q. Wilson.

Criminology Can the can, The Economist

Kees Keizer and his colleagues at the University of Groningen deliberately created such settings as a part of a series of experiments designed to discover if signs of vandalism, litter and low-level lawbreaking could change the way people behave.
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The most dramatic result, though, was the one that showed a doubling in the number of people who were prepared to steal in a condition of disorder. In this case an envelope with a â‚¬5 ($6) note inside (and the note clearly visible through the address window) was left sticking out of a post box. In a condition of order, 13% of those passing took the envelope (instead of leaving it or pushing it into the box). But if the post box was covered in graffiti, 27% did. Even if the post box had no graffiti on it, but the area around it was littered with paper, orange peel, cigarette butts and empty cans, 25% still took the envelope.

The researchers’ conclusion is that one example of disorder, like graffiti or littering, can indeed encourage another, like stealing. Dr Kelling was right. The message for policymakers and police officers is that clearing up graffiti or littering promptly could help fight the spread of crime.

Demystifying the Memristor

Demystifying the memristor

The memristor — short for memory resistor – could make it possible to develop far more energy-efficient computing systems with memories that retain information even after the power is off, so there’s no wait for the system to boot up after turning the computer on. It may even be possible to create systems with some of the pattern-matching abilities of the human brain.
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By providing a mathematical model for the physics of a memristor, the team makes possible for engineers to develop integrated circuit designs that take advantage of its ability to retain information.

“This opens up a whole new door in thinking about how chips could be designed and operated,” Williams says.

Engineers could, for example, develop a new kind of computer memory that would supplement and eventually replace today’s commonly used dynamic random access memory (D-RAM). Computers using conventional D-RAM lack the ability to retain information once they are turned off. When power is restored to a D-RAM-based computer, a slow, energy-consuming “boot-up” process is necessary to retrieve data stored on a magnetic disk required to run the system.

Looking for Signs of Dark Matter Over Antarctica

Dark Matter Proof Found Over Antarctica?

High-energy electrons captured over Antarctica could reveal the presence of a nearby but mysterious astrophysical object that’s bombarding Earth with cosmic rays, researchers say. Or the electrons may be the long-awaited physical evidence of elusive dark matter.

Either way, the unusual particles are exciting for astrophysicists, who say they could someday confirm or deny decades of unproven theories. “In the first case, we have now seen for the first time a nearby source of cosmic rays.
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Cosmic rays are not beams per se but are any protons, electrons, and other subatomic particles that careen toward Earth from a variety of sources, including the supernova explosions that mark the deaths of stars.

Most of the cosmic electrons that reach Earth are low-energy, because the highest-energy ones fizzle the fastest and don’t last long enough to get here.

How Bleach Kills Bacteria

Developed more than 200 years ago and found in households around the world, chlorine bleach is among the most widely used disinfectants, yet scientists never have understood exactly how the familiar product kills bacteria. In fact, Hypochlorite, the active ingredient of household bleach, attacks essential bacterial proteins, ultimately killing the bugs.

“As so often happens in science, we did not set out to address this question,” said Jakob, an associate professor of molecular, cellular and developmental biology. “But when we stumbled on the answer midway through a different project, we were all very excited.”

Jakob and her team were studying a bacterial protein known as heat shock protein 33 (Hsp33), which is classified as a molecular chaperone. The main job of chaperones is to protect proteins from unfavorable interactions, a function that’s particularly important when cells are under conditions of stress, such as the high temperatures that result from fever.

“At high temperatures, proteins begin to lose their three-dimensional molecular structure and start to clump together and form large, insoluble aggregates, just like when you boil an egg,” said lead author Jeannette Winter, who was a postdoctoral fellow in Jakob’s lab. And like eggs, which once boiled never turn liquid again, aggregated proteins usually remain insoluble, and the stressed cells eventually die.

Jakob and her research team figured out that bleach and high temperatures have very similar effects on proteins. Just like heat, the hypochlorite in bleach causes proteins to lose their structure and form large aggregates.

These findings are not only important for understanding how bleach keeps our kitchen countertops sanitary, but they may lead to insights into how we fight off bacterial infections. Our own immune cells produce significant amounts of hypochlorite as a first line of defense to kill invading microorganisms. Unfortunately, hypochlorite damages not just bacterial cells, but ours as well. It is the uncontrolled production of hypochlorite acid that is thought to cause tissue damage at sites of chronic inflammation.

How did studying the protein Hsp33 lead to the bleach discovery? The researchers learned that hypochlorite, rather than damaging Hsp33 as it does most proteins, actually revs up the molecular chaperone. When bacteria encounter the disinfectant, Hsp33 jumps into action to protect bacterial proteins against bleach-induced aggregation.

“With Hsp33, bacteria have evolved a very clever system that directly senses the insult, responds to it and increases the bacteria’s resistance to bleach,” Jakob said.

New Supercomputer for Science Research

“Jaguar is one of science’s newest and most formidable tools for advancement in science and engineering,” said Dr. Raymond L. Orbach, DOE.s Under Secretary for Science. The new capability will be added to resources available to science and engineering researchers in the USA.

80 percent of the Leadership Computing Facility resources are allocated through the United States Department of Energy’s Innovative and Novel Computational Impact on Theory and Experiment (INCITE) program, a competitively selected, peer reviewed process open to researchers from universities, industry, government and non-profit organizations. Scientists and engineers at DOE’s Oak Ridge National Laboratory are finding an increasing variety of uses for the Cray XT system. A recent report identified 10 breakthroughs in U.S. computational science during the past year. Six of the breakthroughs involved research conducted with the Jaguar supercomputer, including a first-of-its-kind simulation of combustion processes that will be used to design more efficient automobile engines. Read the computational science report. Read full press release.

ORNL’s Jaguar fastest computer for science research

Jaguar will be used for studies of global climate change, as well as development of alternative energy sources and other types of scientific problem-solving that previously could not be attempted.

Zacharia said ORNL’s Jaguar was upgraded by adding 200 Cray XT5 cabinets – loaded with AMD quadcore processors and Cray SeaStar interconnects – to the computer’s existing 84 Cray XT4 cabinets. The combined machine resulted in the new standard for computational science.

The peak operating speed is apparently just below that of Los Alamos National Laboratory’s IBM Roadrunner system, which is designed for 1.7 petaflops. But the Jaguar reportedly has triple the memory of Roadrunner and much broader research potential.
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Because the Jaguar has come online sooner than expected, Zacharia said an alert was sent to top U.S. scientists inviting them to apply for early access to the Oak Ridge computer. Their scientific proposals will be reviewed on an accelerated timetable, he said.

The peak capability of 1.64 petaflops is attributed to 1.384 petaflops from the new Cray XT5, combined with 0.266 petaflops from the existing Cray XT4 system, Zacharia said.

How fast is a quadrillion calculations per second? “One way to understand the speed is by analogy,” Zacharia said recently. “It would take the entire population of the Earth (more than 6 billion people), each of us working a handheld calculator at the rate of one second per calculation, more than 460 years to do what Jaguar at a quadrillion can do in one day.”

Genes Counter a Bacterial Attack

Gene against bacterial attack unravelled

Humans have an innate defence system against deadly bacteria. However, how the step from gene to anti-bacterial effect occurs in the body is not yet known. To date, B. Pseudomallei, a bacterium suitable for bioweapons, had managed to elude medics. It can remain hidden in the human body for many years without being detected by the immune system. The bacteria can suddenly become activated and spread throughout the body, resulting in the patient dying from blood poisoning. AMC physician Joost Wiersinga and the Laboratory for Experimental Internal Medicine discovered which gene-protein combination renders the lethal bacteria B. pseudomallei harmless.

Wiersinga focussed on the so-called Toll-like receptors. These are the proteins that initiate the fight against pathogens. There are currently ten known Toll-like receptors which are located on the outside of immune cells, our body’s defence system. The toll-like receptors jointly function as a 10-figure alarm code. Upon coming into contact with the immune cell each bacterium enters its own Toll code. For known pathogens this sets off an alarm in the immune system and the defence mechanism is activated. Yet B. pseudomallei fools the system by entering the code of a harmless bacterium. As a result the body’s defence system remains on standby.

Yet some people are resistant: they become infected but not ill. Wiersinga found a genetic cause for this resistance. He discovered which toll receptor can fend off B. pseudomallei. He did this by rearing mice DNA in which the gene for Toll2 production was switched on and off. ‘The group where the gene for Toll2 was switched off, survived the bacterial infection’, says Wiersinga. ‘The other receptor that we investigated, Toll4, had no effect – even though for the past ten years medics had regarded this as the most important receptor.’ The ultimate aim of this study is to develop a vaccine.

PLoS paper: MyD88 Dependent Signaling Contributes to Protective Host Defense against Burkholderia pseudomallei

Magnetic Portals Connect Sun and Earth

Magnetic Portals Connect Sun and Earth by Dr. Tony Phillips

During the time it takes you to read this article, something will happen high overhead that until recently many scientists didn’t believe in. A magnetic portal will open, linking Earth to the sun 93 million miles away. Tons of high-energy particles may flow through the opening before it closes again, around the time you reach the end of the page.

“It’s called a flux transfer event or ‘FTE,'” says space physicist David Sibeck of the Goddard Space Flight Center. “Ten years ago I was pretty sure they didn’t exist, but now the evidence is incontrovertible.”
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Researchers have long known that the Earth and sun must be connected. Earth’s magnetosphere (the magnetic bubble that surrounds our planet) is filled with particles from the sun that arrive via the solar wind and penetrate the planet’s magnetic defenses. They enter by following magnetic field lines that can be traced from terra firma all the way back to the sun’s atmosphere.

“We used to think the connection was permanent and that solar wind could trickle into the near-Earth environment anytime the wind was active,” says Sibeck. “We were wrong. The connections are not steady at all. They are often brief, bursty and very dynamic.”
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On the dayside of Earth (the side closest to the sun), Earth’s magnetic field presses against the sun’s magnetic field. Approximately every eight minutes, the two fields briefly merge or “reconnect,” forming a portal through which particles can flow. The portal takes the form of a magnetic cylinder about as wide as Earth.

See more posts on scientific inquiry and scientists advancing our understanding of how things work.