Ancient Bones That Tell a Story of Compassion

While it is a painful truism that brutality and violence are at least as old as humanity, so, it seems, is caring for the sick and disabled.

And some archaeologists are suggesting a closer, more systematic look at how prehistoric people — who may have left only their bones — treated illness, injury and incapacitation. Call it the archaeology of health care.

The case that led Lorna Tilley and Marc Oxenham of Australian National University in Canberra to this idea is that of a profoundly ill young man who lived 4,000 years ago in what is now northern Vietnam and was buried, as were others in his culture, at a site known as Man Bac.

Almost all the other skeletons at the site, south of Hanoi and about 15 miles from the coast, lie straight. Burial 9, as both the remains and the once living person are known, was laid to rest curled in the fetal position. When Ms. Tilley, a graduate student in archaeology, and Dr. Oxenham, a professor, excavated and examined the skeleton in 2007 it became clear why. His fused vertebrae, weak bones and other evidence suggested that he lies in death as he did in life, bent and crippled by disease.

They gathered that he became paralyzed from the waist down before adolescence, the result of a congenital disease known as Klippel-Feil syndrome. He had little, if any, use of his arms and could not have fed himself or kept himself clean. But he lived another 10 years or so.

They concluded that the people around him who had no metal and lived by fishing, hunting and raising barely domesticated pigs, took the time and care to tend to his every need.

“There’s an emotional experience in excavating any human being, a feeling of awe,” Ms. Tilley said, and a responsibility “to tell the story with as much accuracy and humanity as we can.”

This case, and other similar, if less extreme examples of illness and disability, have prompted Ms. Tilley and Dr. Oxenham to ask what the dimensions of such a story are, what care for the sick and injured says about the culture that provided it.

The archaeologists described the extent of Burial 9’s disability in a paper in Anthropological Science in 2009. Two years later, they returned to the case to address the issue of health care head on. “The provision and receipt of health care may therefore reflect some of the most fundamental aspects of a culture,” the two archaeologists wrote in The International Journal of Paleopathology.

And earlier this year, in proposing what she calls a “bioarchaeology of care,” Ms. Tilley wrote that this field of study “has the potential to provide important — and possibly unique — insights into the lives of those under study.” In the case of Burial 9, she says, not only does his care indicate tolerance and cooperation in his culture, but suggests that he himself had a sense of his own worth and a strong will to live. Without that, she says, he could not have stayed alive.

Why Music Moves Us

Universal emotions like anger, sadness and happiness are expressed nearly the same in both music and movement across cultures, according to new research.

The researchers found that when Dartmouth undergraduates and members of a remote Cambodian hill tribe were asked to use sliding bars to adjust traits such as the speed, pitch, or regularity of music, they used the same types of characteristics to express primal emotions. What’s more, the same types of patterns were used to express the same emotions in animations of movement in both cultures.

"The kinds of dynamics you find in movement, you find also in music and they’re used in the same way to provide the same kind of meaning," said study co-author Thalia Wheatley, a neuroscientist at Dartmouth University.

The findings suggest music’s intense power may lie in the fact it is processed by ancient brain circuitry used to read emotion in our movement.

"The study suggests why music is so fundamental and engaging for us," said Jonathan Schooler, a professor of brain and psychological sciences at the University of California at Santa Barbara, who was not involved in the study. "It takes advantage of some very, very basic and, in some sense, primitive systems that understand how motion relates to emotion."

Universal emotions

Why people love music has been an enduring mystery. Scientists have found that animals like different music than humans and that brain regions stimulated by food, sex and love also light up when we listen to music. Musicians even read emotions better than nonmusicians.

Past studies showed that the same brain areas were activated when people read emotion in both music and movement. That made Wheatley wonder how the two were connected.

To find out, Wheatley and her colleagues asked 50 Dartmouth undergraduates to manipulate five slider bars to change characteristics of an animated bouncy ball to make it look happy, sad, angry, peaceful or scared.

"We just say ‘Make Mr. Ball look angry or make Mr. Ball look happy,’" she told LiveScience.

To create different emotions in “Mr. Ball,” the students could use the slider bars to affect how often the ball bounced, how often it made big bounces, whether it went up or down more often and how smoothly it moved.

Another 50 students could use similar slider bars to adjust the pitch trajectory, tempo, consonance (repetition), musical jumps and jitteriness of music to capture those same emotions.

The students tended to put the slider bars in roughly the same positions whether they were creating angry music or angry moving balls.

To see if these trends held across cultures, Wheatley’s team traveled to the remote highlands of Cambodia and asked about 85 members of the Kreung tribe to perform the same task. Kreung music sounds radically different from Western music, with gongs and an instrument called a mem that sounds a bit like an insect buzzing, Wheatley said. None of the tribes’ people had any exposure to Western music or media, she added.

Interestingly, the Kreung tended to put the slider bars in roughly the same positions as Americans did to capture different emotions, and the position of the sliders was very similar for both music and emotions.

The findings suggest that music taps into the brain networks and regions that we use to understand emotion in people’s movements. That may explain why music has such power to move us — it’s activating deep-seated brain regions that are used to process emotion, Wheatley said.

"Emotion is the same thing no matter whether it’s coming in through our eyes or ears," she said.

Hypertension traced to source in brain

When the heart works too hard, the brain may be to blame, says new Cornell research that is changing how scientists look at high blood pressure (hypertension). The study, published in the Journal of Clinical Investigation in November, traces hypertension to a newfound cellular source in the brain and shows that treatments targeting this area can reverse the disease.

In what peer reviewers are calling “a new paradigm” for tackling the worldwide hypertension epidemic, this insight into its roots could give hope to the billion people it currently afflicts. Hypertension occurs when the force of blood against vessel walls grows strong enough to potentially cause such problems as heart attack, stroke and heart or kidney disease. The heart pumps harder, and often the hormone angiotensin-II (AngII) gets the pressure cooking by triggering nerve cells that constrict blood vessels.

"We knew the central nervous system orchestrates this process, and now we’ve found the conductor," said Robin Davisson, the Andrew Dickson White Professor of Molecular Physiology with a joint appointment at Cornell’s College of Veterinary Medicine and Weill Cornell Medical College.

Two-thirds of Americans have hypertension, which is the leading cause of North America’s No. 1 killer: heart disease, according to the Centers for Disease Control and Prevention.

Davisson’s lab traced neurochemical signals back to endoplasmic reticulum (ER), the protein factory and stress-management control center in every cell. If something goes wrong in a cell, the ER activates processes to adapt to the stress. Long-term ER stress can cause chronic disease, and several stressors that ER responds to have been connected to hypertension. Davisson’s lab found that high levels of AngII put stress on the ER, which responds by triggering the cascade of neural and hormonal signals that start hypertension.

But not just any cell’s ER can conduct this complex orchestra. Those that can trigger the signal cascade are clustered near the bottom of the brain in a gatelike structure called the subfornical organ (SFO). Unlike most of the brain, the SFO hangs outside a protective barrier that keeps most circulating particles from entering the brain. The SFO can interact with particles like AngII that are too big to cross through and can also communicate with the brain’s inner chambers.

This is good news for developing therapies—because the SFO sits outside the barrier, it can be reached through such normal treatment routes as pills or injections rather than riskier brain procedures. Davisson’s lab showed that treatments that inhibit ER stress in the SFO can completely stop AngII-based hypertension and lower blood pressure to normal levels.

"Our work provides the first evidence that higher levels of AngII cause ER stress in the SFO, that this causes hypertension, and that we can do something about it," said Davisson. "This finding may also suggest a role for ER stress in hypertension types that don’t involve AngII, like some spontaneous or genetic forms."

Inspired by the paradigm shift that this study has sparked, the editors of the Journal of Clinical Investigation published a commentary concluding that this discovery “opens new avenues for investigation and may lead to new therapeutic approaches for this disease.”

Brain imaging identifies bipolar risk

Researchers from the Black Dog Institute and University of NSW have used brain imaging technology to show that young people with a known genetic risk of bipolar but no clinical signs of the condition have clear and quantifiable differences in brain activity when compared to controls.

“We found that the young people who had a parent or sibling with bipolar disorder had reduced brain responses to emotive faces, particularly a fearful face. This is an extremely promising breakthrough,” says study leader Professor Philip Mitchell.

Affecting around 1 in 75 Australians, bipolar disorder involves extreme and often unpredictable fluctuations in mood. The mood swings and associated behaviours such as disinhibited behaviour, aggression and severe depression, have a significant impact on day-to-day life, careers and relationships. Bipolar has the highest suicide rate of all psychiatric disorders.

“We know that bipolar is primarily a biological illness with a strong genetic influence but triggers are yet to be understood. Being able to identify young people at risk will enable implementation of early intervention programs, giving them the best chance for a long and happy life,” says Prof Mitchell.

Researchers used functional MRI to visualise brain activity when participants were shown pictures of happy, fearful or calm (neutral) human faces. Results showed that those with a genetic risk of bipolar displayed significantly reduced brain activity in a specific part of the brain known to regulate emotional responses.

“Our results show that bipolar disorder may be linked to a dysfunction in emotional regulation and this is something we will continue to explore,” Professor Mitchell said.

“And we now have an extremely promising method of identifying children and young people at risk of bipolar disorder.”

 “We expect that early identification will significantly improve outcomes for people that go on to develop bipolar disorder, and possibly even prevent onset in some people.”

Results are published this week in Biological Psychiatry and come from the NHMRC-funded ‘Kids and Sibs study’, the biggest research study in the world focusing on genetic and environmental aspects of bipolar disorder. Based at the Black Dog Institute, the trial is still recruiting.

Hybrid tunnel may help guide severed nerves back to health

Building a tunnel made up of both hard and soft materials to guide the reconnection of severed nerve endings may be the first step toward helping patients who have suffered extensive nerve trauma regain feeling and movement, according to a team of biomedical engineers.

"Nerve injury in both central nervous system and peripheral nervous system is a major health problem," said Mohammad Reza Abidian, assistant professor of biomedical engineering, Penn State. "According to the National Spinal Cord Injury Statistical Center, there are approximately 290,000 individuals in the US who suffer from spinal cord injuries with about 12,000 new injuries occurring each year."

Spontaneous nerve regeneration is limited to small lesions within the injured peripheral nerve system and is actively suppressed within central nervous system. When a nerve in the peripheral nervous system is cut slightly, nerve endings can regenerate and reconnect. However, if the distance between the two endings is too far, the growth can go off course and fail to connect.

The researchers, who published their results in the current issue of Advanced Healthcare Materials, developed a novel hybrid conduit that consisted of a soft material, called a hydrogel, as an external wall along with an internal wall made of an electrically-active conducting polymer to serve as a tunnel that guides the regrowth and reconnection of the severed nerve endings.

Abidian said that the method could offer advantages over current surgeries that are used to reconnect severed nerves.

"Autografts are currently the gold standard for bridging nerve gaps," said Abidian. "This is an operation that takes the nerve from another portion of the body — for instance — from a tendon, and then it is grafted onto the injured nerve."

However, the operation can be painful and there are often mismatches in size between the severed nerve endings and the new grafted portion of the nerve, Abidian said.

New immune therapy successfully treats brain tumors in mice

Using an artificial protein that stimulates the body’s natural immune system to fight cancer, a research team at Duke Medicine has engineered a lethal weapon that kills brain tumors in mice while sparing other tissue. If it can be shown to work in humans, it would overcome a major obstacle that has hampered the effectiveness of immune-based therapies.

The protein is manufactured with two arms – one that exclusively binds to tumor cells and another that snags the body’s fighter T-cells, spurring an attack on the tumor. In six out of eight mice with brain tumors, the treatment resulted in cures, according to findings published Dec. 17, 2012, in the Proceedings of the National Academy of Sciences.

"This work represents a revival of a somewhat old concept that targeting cancer with tumor-specific antigens may well be the most effective way to treat cancer without toxicity," said senior author John H. Sampson, M.D., PhD, a neurosurgeon at The Preston Robert Tisch Brain Tumor Center at Duke. "But there have been problems with that approach, especially for brain tumors. Our therapeutic agent is exciting, because it acts like Velcro to bind T-cells to tumor cells and induces them to kill without any negative effects on surrounding normal tissues."

Sampson and colleagues focused on the immune approach in brain tumors, which are notoriously difficult to treat. Despite surgery, radiation and chemotherapy, glioblastomas are universally fatal, with a median survival of 15 months.

Immunotherapies, in which the body’s B-cells and T-cells are triggered to attack tumors, have shown promise in treating brain and other cancers, but have been problematic in clinical use. Treatments have been difficult to administer at therapeutic doses, or have spurred side effects in which the immune system also attacks healthy tissue and organs.

Working to overcome those pitfalls, the Duke-led researchers designed a kind of connector - an artificial protein called a bispecific T-cell engager, or BiTE – that tethers the tumor to its killer. Their newly engineered protein includes fractions of two separate antibodies, one that recruits and engages the body’s fighter T-cells and one that expressly homes in on an antigen known as EGFRvIII, which only occurs in cancers.

Once connected via the new bispecific antibody, the T-cells recognize the tumor as an invader, and mount an attack. Normal tissue, which does not carry the tumor antigen, is left unscathed.

New form of cell division found

Researchers at the University of Wisconsin Carbone Cancer Center have discovered a new form of cell division in human cells.

They believe it serves as a natural back-up mechanism during faulty cell division, preventing some cells from going down a path that can lead to cancer.

"If we could promote this new form of cell division, which we call klerokinesis, we may be able to prevent some cancers from developing," says lead researcher Dr. Mark Burkard, an assistant professor of hematology-oncology in the department of medicine at the UW School of Medicine and Public Health.

Burkard presented the finding on Monday, Dec. 17 at the annual meeting of the American Society for Cell Biology in San Francisco.

(View a short video of the process here)