Monday, October 18, 2010

WORLD IS FULL OF DARKNESS, REFLECTED IN THE PHYSIOLOGY OF THE HUMAN RETINA

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Physicists and neuroscientists from the University of Pennsylvania have linked the cell structure of the retina to the light and dark contrasts of the natural world, demonstrating the likelihood that the neural pathways humans use for seeing are adapted to best capture the world around us.

Researchers found that retinal ganglion cells that see darkness are more numerous and cluster closer together than those that see light, corresponding to the fact that the natural world contains more dark spots than light. Now physicists, and not just pessimists, see the world for the dark place it is.

The results suggest that the brain’s separation of retinal circuitry into off and on mosaics that separately process dark and bright spots allows for structural adaptation to the natural scenes humans must see.

The team took the study a step further by constructing artificial images that matched the characteristics of the natural world and by testing what sorts of off and on mosaics best represented information from these images. According to the authors, the total flow of information peaked for mosaics with more densely clustered off cells, as in the human retina, suggesting that human vision has evolved to efficiently represent visual information in the natural world.

Researchers looked at the physiology of the retinal ganglion cells whose job it is to respond to a dark spot on a brighter background, simply called off cells, wondering why the brain would have clusters of off cells and not an even distribution across the retina. In addition to being more numerous and branching together in dense, bushy clusters, they also have smaller dendritic fields than the cells responsible for seeing light spots. By branching together more densely in clusters, they collect more synapses per visual angle. Thus, researchers concluded that the retina devotes more resources to processing dark contrasts, a natural capability reflected in the fact that there is more dark information in the world around us.

Researchers tested the hypothesis by measuring the spatial contrasts in natural images and quantifying the distribution of lightness and darkness. At all scales, the authors found that natural images contain relatively more dark contrasts than light.

“Photoreceptors respond to light,” Vijay Balasubramanian, professor of physics and the study’s lead author, said. “But a couple of layers deeper down in the retina, cells are responding to changes and differences in the amount of light across the image. The eye is not a digital camera, recording little pixels. The eye doesn’t do that. The eye tells the brain that there are differences in light between neighboring points. The brain learns about contrast. And in this case, there is about twice as much brain activity responding to darker spots.”

The team confirmed this across a range of spatial scales and traced the origin of this phenomenon to the statistical structure of natural scenes. Researchers showed that the optimal mosaics for encoding natural images are also asymmetric, with off elements smaller and more numerous, thus matching retinal structure. Finally, the concentration of synapses within a dendritic field matches the information content, suggesting a simple principle to connect a concrete fact of neuroanatomy with the abstract concept of “information”: equal synapses for equal bits.

Researchers were interested in how the visual system is adapted to the physical structure of the world, an assumption that makes sense from an evolutionary standpoint. The physics of the natural world should correspond to the processing capabilities of the brain and there are many observable incidences of this phenomenon in the human and animal world. For example, frogs eat flies. That fact predicted that frog’s eye contains “fly detectors.” Flies, in turn, track potential mates in mid-air, predicting specialized neural fly circuits that detect other flies.

This study demonstrates the opposite case. Here, a particular feature of the human neural circuitry predicted a surprising property of the visual environment.

(Photo: Univ. of Pennsylvania)

University of Pennsylvania

DINOSAURS SIGNIFICANTLY TALLER THAN PREVIOUSLY THOUGHT

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It might seem obvious that a dinosaur’s leg bone connects to the hip bone, but what came between the bones has been less obvious. Now, researchers at the University of Missouri and Ohio University have found that dinosaurs had thick layers of cartilage in their joints, which means they may have been considerably taller than previously thought. The study has been published in the journal PLoS-ONE (Public Library of Science).

“Our study of the limbs of modern-day relatives of dinosaurs shows that dinosaurs were significantly taller than original estimates,” said Casey Holliday, lead author of the study and an anatomy professor in the MU School of Medicine. “The ends of many dinosaurs’ long bones, which include leg bones such as the femur or tibia, are rounded and rough and lack major articulating structures like condyles, which are bony projections. This indicated that very thick cartilages formed these structures, and therefore the joints themselves, and would have added significant height to certain dinosaurs. This study offers new data into how and why reptiles, and mammals, such as humans, build their joints with such different amounts of bone and cartilage.”

Holliday and Lawrence Witmer, a professor of anatomy at the Ohio University College of Osteopathic Medicine, conducted research on ostriches and alligators, the closest, modern-day relatives of dinosaurs, and then studied the fossilized limbs of different dinosaurs including Tyrannosaurus rex, Allosaurus, Brachiosaurus and Triceratops. The team determined that the lengths of alligators’ and ostriches’ limbs included between 6 and 10 percent cartilage.

Using a “cartilage correction factor,” Holliday determined that many theropod dinosaurs, such as Tyrannosaurus, were only modestly taller whereas ornthischian and sauropod dinosaurs, such as Triceratops and Brachiosaurus, may have been 10 percent taller or more. For example, Brachiosaurus, previously thought to be 42 feet tall, may actually have been more than a foot taller with the additional joint cartilages.

“This study is significant because it shows that bones can’t always speak for themselves,” Witmer said. “To understand how dinosaurs moved, we need to analyze the bones as they were inside their bodies, including their cartilage. The dinosaur bones mounted in museums don’t accurately reflect what the animals actually had in their bodies in life because the cartilage caps were lost along with the other soft tissues. Knowing how much cartilage was lost allows us to better restore the structure of a living dinosaur bone, which then allows us to better understand how dinosaurs moved and lived”

Understanding the structures of the soft tissues in dinosaurs might also have implications for their speed and posture. While an increase in limb length typically means a taller dinosaur, it could also mean a faster or slower animal, depending on how it affects the skeleton, Holliday said. This finding could have major implications on how scientists currently understand dinosaur anatomy.

Dinosaur bones are different than the bones of mammals, including humans. Mammals have small protrusions at the end of each bone that help it connect with another bone at a joint, like two puzzle pieces. The bones are linked by a very thin layer of cartilage, which provides padding in the joint, but often wears down leading to painful conditions like arthritis. Comparatively, dinosaur bones have rounded ends and no obvious way to connect one bone to another. Soft tissue structures like cartilage and muscles leave marks on bones, which enable paleontologists to make sophisticated determinations about a dinosaur’s physical attributes.

Alligators have smooth, rounded bones while young ostriches have rough surfaces on their bones that mark where blood vessels feed large cartilaginous structures in the joints. Both characteristics are similar to dinosaur bones.

Holliday’s team dissected the alligator and ostrich bones and made casts of the bones with cartilage. The team then removed the cartilage and compared the bones to the casts. The bones without the cartilage were 4 to 10 percent smaller. From the evidence, Holliday and his research team concluded that certain dinosaurs had a significant amount of cartilage, and thus, were taller than original estimates. In the future, Holliday hopes to collaborate with MU veterinarians to study how and why different vertebrates build their joints with different proportions of cartilage and bone.

Ohio University

NEANDERTHALS HAD FEELINGS TOO

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Pioneering new research by archaeologists at the University of York suggests that Neanderthals belied their primitive reputation and had a deep seated sense of compassion.

A team from the University’s Department of Archaeology took on the ‘unique challenge’ of charting the development of compassion in early humans.

The researchers examined archaeological evidence for the way emotions began to emerge in our ancestors six million years ago and then developed from earliest times to more recent humans such as Neanderthals and modern people like ourselves. The research by Dr Penny Spikins, Andy Needham and Holly Rutherford is published in the journal Time and Mind.

The archaeologists studied archaeological evidence and used this to propose a four stage model for the development of human compassion. It begins six million years ago when the common ancestor of humans and chimpanzees experienced the first awakenings of an empathy for others and motivation to ‘help’ them, perhaps with a gesture of comfort or moving a branch to allow them to pass.

The second stage from 1.8 million years ago sees compassion in Homo erectus beginning to be regulated as an emotion integrated with rational thought. Care of sick individuals represented an extensive compassionate investment while the emergence of special treatment of the dead suggested grief at the loss of a loved one and a desire to soothe others feelings.

In Europe between around 500,000 and 40,000 years ago, early humans such as Homo heidelbergensis and Neanderthals developed deep-seated commitments to the welfare of others illustrated by a long adolescence and a dependence on hunting together. There is also archaeological evidence of the routine care of the injured or infirm over extended periods. These include the remains of a child with a congenital brain abnormality who was not abandoned but lived until five or six years old and those of a Neanderthal with a withered arm, deformed feet and blindness in one eye who must have been cared for, perhaps for as long as twenty years..

In modern humans starting 120,000 years ago, compassion was extended to strangers, animals, objects and abstract concepts.

Dr Penny Spikins, who led the research, said that new research developments, such as neuro-imaging, have enabled archaeologists to attempt a scientific explanation of what were once intangible feelings of ancient humans. She added that this research was only the first step in a much needed prehistoric archaeology of compassion.

“Compassion is perhaps the most fundamental human emotion. It binds us together and can inspire us but it is also fragile and elusive. This apparent fragility makes addressing the evidence for the development of compassion in our most ancient ancestors a unique challenge, yet the archaeological record has an important story to tell about the prehistory of compassion,” she said.

“We have traditionally paid a lot of attention to how early humans thought about each other, but it may well be time to pay rather more attention to whether or not they ‘cared’.”

University of York

IN PARKINSON'S DISEASE, BRAIN CELLS ABANDON MITOCHONDRIA

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In a study that sheds new light on the causes of Parkinson's disease, researchers report that brain cells in Parkinson's patients abandon their energy-producing machinery, the mitochondria. A shutdown in fuel can have devastating effects on brain cells, which consume roughly 20 percent of the body's energy despite making up only 2 percent of body weight.

The findings indicate that boosting the mitochondria with FDA approved drugs early on may prevent or delay the onset of Parkinson's. The study was published in the one-year anniversary issue of the journal Science Translational Medicine, on Wednesday October 6 2010. Science Translational Medicine is published by AAAS, the nonprofit science society.

Affecting roughly 5 million people worldwide, Parkinson's disease is a relentless condition that starts killing dopamine neurons in the brain many years before the onset of hallmark symptoms like tremors, muscle rigidity and slow movements. Thus, much-needed drugs to slow or halt the disease would have the greatest benefit for patients if they are given early on, before too many dopamine neurons die.

Clemens Scherzer from Brigham and Women's Hospital and Harvard Medical School, along with an international team of researchers, now show that a root cause of Parkinson's disease may lie in 10 gene sets related to energy production that spur neurons in the brain to "divorce" their mitochondria and related energy-producing pathways.

These gene sets are controlled by a master regulator--the PGC-1alpha gene. Moreover, abnormal expression of these genes likely occurs during the initial stages of Parkinson's disease, long before the onset of symptoms, the study shows. Targeting PGC-1alpha may thus be an effective way to slow down or halt the earliest stages of Parkinson's, staving off permanent damage and neuronal loss.

"The most exciting result from our study for me is the discovery of PGC-1alpha as a new therapeutic target for early intervention in Parkinson's disease. PGC-1alpha is a master switch that activates hundreds of mitochondrial genes, including many of those needed to maintain and repair the power plants in the mitochondria," Scherzer said.

FDA-approved medications that activate that PGC-1alpha are already available for widespread diseases like diabetes. These medications may jumpstart the development of new Parkinson's drugs; instead of having to start from scratch, pharmaceutical companies may be able to dust off their drug libraries and find look-alike drugs capable of targeting PGC-1alpha in the brain.

"As we wrap up our first year of publishing the journal, the new study from Zheng et al. exemplifies the goal of Science Translational Medicine, applying knowledge and technology from different fields-such as neuroscience, genomics and bioinformatics-to achieve new discoveries," said Editor Katrina Kelner.

Previous studies have linked defects in mitochondrial activity to Parkinson's disease, but they generally have not provided such a comprehensive, specific set of genes as Scherzer and colleagues now report. The researchers analyzed a part of the brain called the substantia nigra in 185 tissue samples from deceased Parkinson's patients.

The substantia nigra (Latin for "black substance") contains dopamine-producing neurons. Scherzer and colleagues used a laser beam to precisely cut out the dopamine neurons that are abnormal in Parkinson's. Next, the team looked at gene activity in these dopamine neurons and identified gene sets--groups of genes involved in one biological process--that are associated with Parkinson's disease. At the end of this tour-de-force analysis, 10 gene sets linked to Parkinson's emerged. All of these gene sets had a common thread—the master regulator gene PGC-1alpha.

The 10 gene sets encode proteins responsible for cellular processes related to mitochondrial function and energy production. Suppressing these genes is likely to severely damage components required for brain energy metabolism. One of these components is the electron transport chain; a set of reactions controlled by mitochondria that generates the energy cells need to function. Other studies have hinted that one of the five complexes making up the electron transport chain malfunctions in Parkinson's. Yet, Scherzer and colleagues found that not just one, but virtually all of the components needed by mitochondria to build the electron transport chain are deficient.

Why would the brain, being so highly energy dependent, abandon its entire energy-producing apparatus? That seems to be the core mystery of Parkinson's disease. Some think that mitochondrial activity may be affected by a combination of genes and the environment.

"I believe that environmental chemicals, risk genes, and aging--each having a small effect when taken separately--in combination may lead to the pervasive electron transport chain deficit we found in common Parkinson's disease and to which dopamine neurons might be intrinsically more susceptible," said senior author Clemens Scherzer, Assistant Professor of Neurology at Harvard Medical School.

AAAS

GREATEST WARMING IS IN THE NORTH, BUT BIGGEST IMPACT ON LIFE IS IN THE TROPICS

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In recent decades documented biological changes in the far Northern Hemisphere have been attributed to global warming, changes from species extinctions to shifting geographic ranges. Such changes were expected because warming has been fastest in the northern temperate zone and the Arctic.

But new research published in the Oct. 7 edition of Nature adds to growing evidence that, even though the temperature increase has been smaller in the tropics, the impact of warming on life could be much greater there than in colder climates.

The study focused on ectothermic, or cold-blooded, organisms (those whose body temperature approximates the temperature of their surroundings). Researchers used nearly 500 million temperature readings from more than 3,000 stations around the world to chart temperature increases from 1961 through 2009, then examined the effect of those increases on metabolism.

"The expectation was that physiological changes would also be greatest in the north temperate-Arctic region, but when we ran the numbers that expectation was flipped on its head," said lead author Michael Dillon, an assistant professor of zoology and physiology at the University of Wyoming.

Metabolic changes are key to understanding some major impacts of climate warming because a higher metabolic rate requires more food and more oxygen, said co-author Raymond Huey, a University of Washington biology professor. If, for example, an organism has to spend more time eating or conserving energy, it might have less time and energy for reproduction.

"Metabolic rate tells you how fast the animal is living and thus its intensity of life," Huey said.

Using a well-documented, century-old understanding that metabolic rates for cold-blooded animals increase faster the warmer the temperature, the researchers determined that the effects on metabolism will be greatest in the tropics, even though that region has the smallest actual warming. Metabolic impacts will be less in the Arctic, even though it has shown the most warming. In essence, organisms in the tropics show greater effects because they start at much higher temperatures than animals in the Arctic.

Dillon and co-author George Wang of the Max Planck Institute for Developmental Biology in Tübingen, Germany, sifted through temperature data maintained by the National Oceanic and Atmospheric Administration's National Climatic Data Center. They came up with readings from 3,186 stations that met their criteria of recording temperature at least every six hours during every season from 1961 through 2009. The stations, though not evenly spaced, represented every region of the globe except Antarctica.

The data, the scientists said, reflect temperature changes since 1980 that are consistent with other recent findings that show the Earth is getting warmer. Temperatures rose fastest in the Arctic, not quite as fast in the northern temperate zone and even more slowly in the tropics.

"Just because the temperature change in the tropics is small doesn't mean the biological impacts will be small," Huey said. "All of the studies we're doing suggest the opposite is true."

In fact, previous research from the University of Washington has indicated that small temperature changes can push tropical organisms beyond their optimal body temperatures and cause substantial stress, while organisms in temperate and polar regions can tolerate much larger increases because they already are used to large seasonal temperature swings.

The scientists say the effects of warming temperatures in the tropics have largely been ignored because temperature increases have been much greater farther north and because so few researchers work in the tropics.

"I think this argues strongly that we need more studies of the impacts of warming on organisms in the tropics," Dillon said.

University of Wyoming

PSYCHOLOGIST FINDS 'SHOCKING' IMPACT ON NAME RECALL

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It's an experience shared by everyone: You run into someone you know, but his or her name escapes you.

Now, Temple psychologist Ingrid Olson has found a way to improve the recall of proper names.

Olson dedicates her research to understanding human memory. In a recent study, she found that electric stimulation of the right anterior temporal lobe of the brain improved the recall of proper names in young adults by 11 percent. Her study appears this month in the journal Neuropsychologia.

"We know a lot about how to make people's memory worse, but we don't know very much about how to make people's memory better," said Olson. "These findings hold promise because they point to possible therapeutic treatments for memory rehabilitation following a stroke or other neurological insult."

Olson is currently conducting a follow-up study in older adults, in collaboration with David Wolk at the University of Pennsylvania's Penn Memory Center. Because memory decline is part of normal aging, the difficulty in remembering proper names is exacerbated as we get older. Olson predicts that the memory gain will be even more significant among the older research subjects because they start with a lower baseline recall level.

For the study, subjects received electric stimulation to their anterior temporal lobes while looking at photos of faces of known or semi-famous people and landmarks. Her findings support previous research suggesting that the anterior temporal lobes are critically involved in the retrieval of people's names. She did not find any improvement in the recall of the names of the landmarks.

The electrical stimulation was delivered using transcranial direct current stimulation (tDCS), a technique by which small electric currents (e.g., 1-2 milliamps) are applied to the scalp via electrodes. Depending on the desired effect, the small currents can either temporarily disrupt or enhance brain functions in a localized brain region.

In recent years, tDCS has been rediscovered as a rehabilitation and research tool. In her work, Olson collaborates with at the University of Pennsylvania's Laboratory of Cognition and Neural Stimulation. Led by Branch Coslett, the group is one of just a few in the country studying the technique.

According to Olson, it is important to distinguish tDCS from electroconvulsive therapy (ECT), made famous in movies such as One Flew over the Cuckoo's Nest. ECT is used to treat serious mental illnesses by passing pulses of approximately 1 ampere of electricity into the brain in order to provoke a seizure. By contrast, tDCS uses a much smaller current (e.g. 1-2 milliamps) with effects that typically last just one hour. The technique is painless, and there are no known adverse effects.

"As we age, the connections between the neurons in our brains weaken," said Olson. "In our study, tDCS works by increasing the likelihood that the right neurons will fire at the moment when the research subject is trying to retrieve a particular name," she said.

"One question for further research is whether or not repeating tDCS may lead to longer lasting effects," she said.

(Photo: Temple U.)

Temple University

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