Tuesday, September 7, 2010

WHALE SHARKS MAY PRODUCE MANY LITTERS FROM ONE MATING, PATERNITY TEST SHOWS

0 comentarios
How do female whale sharks meet their perfect mates and go on to produce offspring? While little is known about the reproductive behavior of these ocean-roaming giants, a newly published analysis led by University of Illinois at Chicago biologist Jennifer Schmidt reveals new details about the mating habits of this elusive, difficult-to-study fish.

Schmidt, a UIC associate professor of biological sciences, determined paternity of 29 frozen embryos saved from a female whale shark caught off the coast of Taiwan in 1995. The embryos, studied in collaboration with Professor Shoou-Jeng Joung at the National Taiwan Ocean University, are extremely rare.

The pregnant shark carried a surprisingly large number of embryos -- 304 -- still in the uterus and representing a spectrum of age and development stages ranging from being still egg-encased to developed, near-term animals.

Schmidt and her colleagues spent several years developing DNA genetic markers to study whale sharks, initially for population genetics, but in this study the tool was used to determine paternity.

Shark reproduction is still an emerging science, but what is known suggests that most broods are sired by more than one male. That is not what Schmidt found with this particular female whale shark.

"These differently aged embryos -- itself unusual across animal species -- had the same father," Schmidt said. "We have to be very cautious in drawing conclusions from a single litter, but the data suggest female whale sharks store sperm after a single mating event, and subsequently fertilize their own eggs as they are produced."

If the finding can be supported from analysis of other whale shark litters, Schmidt said, "it would suggest that there is no whale shark breeding ground where large numbers of animals meet to mate, but rather that mating occurs as an isolated event."

Follow-up studies may be serendipity. International protocols protect whale sharks from capture, few are housed in aquariums, and those that are are usually less than 25 years old and not yet sexually mature. Scientists typically study whale sharks at seasonal feeding grounds, but those animals are usually juveniles not mature enough to breed. Rarely are adult females observed in the wild.

"Protections for whale sharks have increased in many parts of the world, yet shark numbers seem to be declining, and the average size is getting smaller," said Mark Meekan, principal research scientist with the Australian Institute of Marine Sciences.

"This is a classic sign of overfishing, where larger, more valuable animals are selectively removed," he said. "Targeted fishing of breeding-age animals in a late-maturing species can be devastating for its survival."

University of Illinois

LEDS PROMISE BRIGHTER FUTURE, NOT NECESSARILY GREENER

0 comentarios
Solid-state lighting pioneers long have held that replacing the inefficient Edison light bulb with more efficient solid-state light-emitting devices (LEDs) would lower electrical usage worldwide, not only “greenly” decreasing the need for new power plants but even permitting some to be decommissioned.

But, in a paper published in the Journal of Physics D, leading LED researchers from Sandia National Laboratories argue for a shift in that view.

“Presented with the availability of cheaper light, humans may use more of it, as has happened over recent centuries with remarkable consistency following other lighting innovations,” said Sandia lead researcher Jeff Tsao. “That is, rather than functioning as an instrument of decreased energy use, LEDs may be instead the next step in increasing human productivity and quality of life.”

The assumption that energy production for lighting will decline as the efficiency of lighting increases is contraindicated by data starting with the year A.D. 1700 that shows light use has remained a constant fraction of per capita gross domestic product as humanity moved from candle to oil to gas to electrical lighting. Thus the societal response to more efficient light production has been a preference to enjoy more light, rather than saving money and energy by keeping the amount of light produced a constant.

“Over the past three centuries, according to well-accepted studies from a range of sources, the world has spent about 0.72 percent of the world’s per capita gross domestic product on artificial lighting,” said Tsao. “This is so for England in 1700, in the underdeveloped world not on the grid and in the developed world using the most advanced lighting technologies. There may be little reason to expect a different future response from our species.”

Far from an example of light gluttony, Tsao said, by increasing the amount of lit work space and bright time, individuals would enjoy the desirable outcome of increasing their creativity and the productivity of their society.

To the question of how much light is enough, says Tsao, no one yet has produced a gold standard for light saturation levels.

While artificial illumination is considerably better now than decades ago, the researchers write, “People might well choose higher illuminances than they do today, particularly to help mitigate losses in visual acuity in an aging world population.” More easily available light also may help reduce seasonal depression brought on by the shorter darker days of winter, and help synchronize biological rhythms, called circadian, that affect human behavior day and night.

As for problems that could occur with too much light — from so-called ‘light pollution’ that bedevils astronomers to biological enzymes that operate better in darkness — Tsao has this to say: “This new generation of solid-state lighting, with our ability to digitally control it much more precisely in time and space, should enable us to preserve dark when we need it.” There is no reason to fear, Tsao says, that advancing capabilities “will keep us perpetually bathed in light.”

Another paper author, Sandia researcher Jerry Simmons points out, “More fuel-efficient cars don’t necessarily mean we drive less; we may drive more. It’s a tension between supply and demand. So, improvements in light-efficient technologies may not be enough to affect energy shortages and climate change. Enlightened policy decisions may be necessary to partner with the technologies to have big impacts.”

Sandia National Laboratories

SYSTEM USES ELECTRICAL TRICKERY ON THE BRAIN TO INDUCE REALISTIC SPACEFLIGHT EFFECTS

0 comentarios

What does it feel like to return to Earth after a long stay in space? Until now, it has been difficult during astronaut training to realistically simulate the dizzying effects the human body can experience.

Dr. Steven Moore leads a research group that has developed a Galvanic vestibular stimulation (GVS) system that safely induces the sensory and mobility disturbances commonly experienced by astronauts after returning to Earth's gravity, making it an excellent operational training tool.

When returning to gravity, these disturbances could affect an astronaut's vision and neurological function, impacting the ability to land a spacecraft. Once on the ground, astronauts often have trouble keeping their balance and walking.

"You can train for spaceflight tasks under normal conditions on Earth, but that will not give you an indication of what an astronaut will feel like," said Moore, a member of the National Space Biomedical Research Institute's (NSBRI) Sensorimotor Adaptation Team. "The GVS system will make mission simulations more realistic. This will be quite useful for astronaut training, especially for astronauts that have not flown before."

The system developed by Moore, who is an associate professor of neurology at Mount Sinai School of Medicine in New York, uses electrodes placed behind the ear to deliver small amounts of electricity to the vestibular nerve, which then sends the signals to the brain, resulting in sensorimotor disturbances.

"We know that GVS is a good model of how microgravity affects astronauts," Moore said. "What we didn't know is how good of an operational analog GVS is for the effects of spaceflight. We now have a validated, ground-based analog for the effects of spaceflight on neurological function that is not just posture, balance and eye movement."

The concept of tricking the brain with Galvanic vestibular stimulation has been around for a long time. However, the system developed by Moore has several unique aspects in addition to simulating spaceflight's effects. First, it uses large electrodes to deliver the stimulus, which have proven to be more comfortable than smaller electrodes. Second, the module, which can deliver up to a 5 milliamp current, is portable and about the size of a box of tissues, making it easy for people to use it while walking.

In order to determine the viability of using GVS as an analog, Moore tested 12 subjects in the Vertical Motion Simulator at NASA Ames Research Center at Moffett Field, Calif. Each subject flew 16 simulated shuttle landings, with the pilots experiencing the GVS analog during eight of the simulations. The subjects included a veteran shuttle commander, NASA test pilots and U.S. Air Force pilots. The results were compared to data collected from more than 100 shuttle landings.

According to Moore, one out of five shuttle landings have been outside the optimal performance range, such as touchdown speed and sink rate. He said the pilots using GVS during landing simulations experienced sensorimotor disturbances similar to the shuttle pilots.

For example, GVS generated a significant increase in touchdown speed consistent with that observed in actual shuttle landings. "Without GVS, they were right on the target – around 204 knots," Moore said. "With GVS, the average speed was pushed up to about 210 knots, which is at the upper limit of the target range."

The study subjects also experienced GVS-induced problems during a routine landing approach braking maneuver that required the pilots to bring the craft from a 20-degree glideslope angle to a 1.5-degree angle. This is a point during actual shuttle landing approaches at which pilots experienced sensorimotor issues and increased gravitational forces from acceleration.

"The GVS stimulation of the nerves is making the simulator pilots think the spacecraft is moving around. We are happy with that result," he said. "GVS induced similar decrements in simulator landings to those during actual shuttle landings."

Even though the research used shuttle landings as the test bed, Moore said the GVS is a viable analog for other space vehicles and operations, such as landing on Mars.

In addition to testing the system's viability as a spaceflight analog, the researchers tested 60 subjects to determine their tolerance to the GVS stimulation during 15- to 20-minute sessions. More than 90 percent of those tested had a high tolerance, and the results showed that GVS stimulation impairs cognitive abilities related to spatial processing. The next step for the researchers is to study whether people have the ability to adapt to the use of GVS over multiple sessions.

The GVS system also has potential use in training aircraft pilots and in preparing people with vestibular disorders for the effects following surgery.

(Photo: Eric Wolfe)

National Space Biomedical Research Institute

WAITING FOR THE RIGHT MOMENT

0 comentarios

Pathogens make themselves feel at home in the human body, invading cells and living off the plentiful amenities on offer. However, researchers at the Max Planck Institute for Infection Biology, Berlin, together with colleagues at Harvard University, reveal an opposite strategy used to ensure infection success. Pathogens can actually delay their entry into cells to ensure their survival. Upon cell contact, bacteria trigger a local strengthening of the cellular skeleton with the aid of signalling molecules, allowing them to remain outside the cell. The researchers also show that this strategy, unknown until now, is used by certain intestinal pathogens as well.

Infection with the sexually transmitted bacterium Neisseria gonorrhoeae can lead to an inflammation of the urogenital tract, the uterus and ovaries. By means of thread-shaped proteins on its surface called pili, the bacterium attaches itself to the cell membrane. Once attached, the bacteria undergo rapid changes of their surface structure to avoid recognition by the host’s immune system. Only during the later stages of infection will the pathogens penetrate cells and occasionally advance into deeper tissues to find further breeding ground.

Until now scientists were firmly focused on understanding the tricks used by these pathogens to enter cells. The results of the Berlin-based researchers suggest, however, that bacteria may spend as much effort in resisting cell entry. Host cells tend to generate tiny vesicles by which they transport bacteria inadvertently into the interior. The researchers have now shed some light on the signals which prevent the bacteria from being ‘swallowed’. Upon fastening themselves to the cell surface, the bacteria induce a sequence of events that results in the strengthening of the cell skeleton directly beneath the point of attachment. The structural protein Actin is transported to attachment sites, where it forms a strong, supportive chain. In tandem, another structural protein Caveolin-1 and the signalling proteins VAV2 and RhoA are recruited to the cell membrane where they play a central role in effectively maintaining N. gonorrhoeae in the extracellular milieu.

These results have opened up new perspectives in understanding the course of infections: "For a long time it was thought that most pathogens strive to enter cells quickly. However, the opposite may be the case. It seems the bacteria prolong their extracellular existence in order to survive", declares Thomas F. Meyer of the Max Planck Institute of Infection Biology. By anchoring to the cell via pili proteins and assembling an underlying support skeleton, the pathogen is buffered against the often inhospitable conditions of the extracellular environment.

By extrapolating their findings to the intestinal bacteria Escherichia coli, the scientists have indicated that the strategy of delaying entry into cells to ensure survival may be widespread among pathogens, possibly even the bacterial agents of meningitis and pneumonia. These newly discovered signalling pathways may therefore have exciting implications for the prevention of infection.

(Photo: Max Planck Institute for Infection Biology)

Max Planck Institute

NO LAUGHING MATTER: LAUGHTER CAN PLAY KEY ROLE IN GROUP DYNAMICS

0 comentarios
Laughter can play key roles in group communication and group dynamics – even when there’s nothing funny going on. That’s according to new research from North Carolina State University that examined the role of laughter in jury deliberations during a capital murder case.

The researchers were given access to the full transcript of jury deliberations in the 2004 Ohio trial of Mark Ducic, a white male charged with two murders and 30 additional counts, largely related to drug violations. “This was a rare opportunity to gain insight into the jury’s deliberative process,” says Dr. Joann Keyton, a professor of communication at NC State and co-author of the study. “As far as we know, this is the only jury transcript available for study from a death penalty case.”

Looking at the transcript, Keyton and her co-author – Dr. Stephenson Beck of North Dakota State University – were struck by the amount of laughter. “This was intriguing,” Keyton says. “We’re interested in how people communicate within a group in order to accomplish a task, and we saw this as an opportunity to explore the role of laughter in how people signal support – or lack of support – for other people’s positions within a group.” Keyton notes that there is very little research on the role of laughter in communication, particularly when divorced from humor.

The researchers learned that laughter could be used as a tool, intentionally and strategically, to control communication and affect group dynamics. For example, one juror was very vocal and made it clear early in the case that she was opposed to the death penalty. In one instance, when that juror agreed with other jury members, one of the other members said “She’s so smart,” resulting in laughter from other members of the group. “That had the effect of further distancing her from the rest of the jury,” Keyton says.

“When juries form, they don’t know each other,” Keyton says. “So part of the jury process is to create relationships within the group – for example, figuring out who thinks like me, who will have the same position I have. There are power dynamics at play.”

The researchers also found that “laughter matters, even when it is a serious group task,” Keyton says. “Laughter is natural, but we try to suppress it in formal settings. So, when it happens, it’s worth closer examination.”

For example, at one point the jury was unclear on whether a sentence related to one of the charges was for 30 days or 30 years. This confusion led to widespread laughter. “The laughter allowed the jurors to release some tension, while also allowing them to acknowledge they had made an error – so they could move forward with that error corrected,” Keyton says.

“Laughter is one way of dealing with ambiguity and tension in situations where a group is attempting to make consequential decisions and informal power dynamics are in play,” Keyton says. “There are very few opportunities to see group decision making, with major consequences, in a public setting,” Keyton explains. “It is usually done in private, such as in corporate board meetings or judicial proceedings. But laughter is something that occurs frequently, and not only because something is funny. Nobody in the jury was laughing at jokes.”

North Carolina State University

NEW STUDY SHOWS HOW TORTOISES, ALLIGATORS THRIVED IN HIGH ARCTIC SOME 50 MILLION YEARS AGO

0 comentarios
A new study of the High Arctic climate roughly 50 million years ago led by the University of Colorado at Boulder helps to explain how ancient alligators and giant tortoises were able to thrive on Ellesmere Island well above the Arctic Circle, even as they endured six months of darkness each year.

The new study, which looked at temperatures during the early Eocene period 52 to 53 million years ago, also has implications for the impacts of future climate change as Arctic temperatures continue to rise, said University of Colorado at Boulder Associate Professor Jaelyn Eberle of the department of geological sciences, lead author of the study.

The team used a combination of oxygen isotope ratios from fossil bone and tooth enamel of mammals, fish and turtles that lived together on Ellesmere Island to estimate the average annual Eocene temperature for the site. They also were able to tease out temperature estimates for the warmest and coldest months of the year, critical data that should help scientists better understand past and future biodiversity in the High Arctic as the climate warms, including the geographical ranges and species richness of animals and plants.

The team concluded the average temperatures of the warmest month on Ellesmere Island during the early Eocene were from 66 to 68 degrees Fahrenheit (19-20 degrees C), while the coldest month temperature was about 32 to 38 degrees F (0-3.5 degrees C). "Our data gathered from multiple organisms indicate it probably did not get below freezing on Ellesmere Island during the early Eocene, which has some interesting implications," she said.

A paper on the subject was published in this month's issue of Earth and Planetary Science Letters. Co-authors included Henry Fricke from Colorado College, John Humphrey and Logan Hackett from the Colorado School of Mines, Michael Newbrey from University of Alberta, Edmonton, and Howard Hutchison from the University California, Berkeley. The National Science Foundation funded the study.

"This is arguably the most comprehensive data set for the early Eocene High Arctic, and certainly explains how alligators and giant tortoises could live on Ellesmere Island some 52 to 53 million years ago," said Eberle, who also is the curator of fossil vertebrates at the University of Colorado Museum of Natural History.

During the Eocene, Ellesmere Island -- which is adjacent to Greenland -- probably was similar to swampy cypress forests in the southeastern United States today, said Eberle. Eocene fossil evidence collected there in recent decades by various teams indicate the lush landscape hosted giant tortoises, aquatic turtles, large snakes, alligators, flying lemurs, tapirs, and hippo-like and rhino-like mammals.

The bone and tooth enamel of vertebrate fossils contains biogenic apatite -- a mineral that is fossilized after the death of living organisms and which can be used as a "flight recorder" to infer paleoclimate conditions. Since all of the fossil materials were from the same stratigraphic layer and locality, the oxygen isotope ratios from the animals are linked to the temperatures of both ingested river water and precipitation at the time, allowing them to better estimate temperatures in the Eocene both annually and seasonally, she said.

"We use the water that the animals were drinking as a proxy for paleotemperature," said Eberle. "In mammal fossils, for example, we can analyze the oxygen isotope ratios in a sequence along the length of a large fossil tooth and estimate the warm-month and cold-month averages during the Eocene because teeth grow year round. When it comes to oxygen isotope values in tooth enamel, what we found for these creatures is that you are what you drink," she said.

The team looked at teeth from a large, hippo-like mammal known as Coryphodon, as well as bones from bowfin fish and shells and bones from aquatic turtles from the Emydidae family, the largest and most diverse family of contemporary pond turtles. While Coryphodon and bowfins grew throughout the year, the turtles exhibited shell growth only during summer months, much like turtles that live today in non-equatorial areas.

"By looking at a host of animals with different physiologies, we were better able to pin down warm- and cold-month temperatures," she said. "Many aspects of biodiversity and species richness are related more to seasonal temperatures and ranges such as cold-month means rather than to mean annual temperature."

Bowfins -- which have a long dorsal fin and powerful jaws -- inhabit a variety of waters today from the Saint Lawrence River drainage in Quebec south to Florida and Texas. The team also compared the ranges of bowfins, aquatic turtles and giant tortoises of today with their ranges in the Eocene to help them estimate temperatures, according to co-author Newbrey, an expert in both contemporary and extinct fishes.

Eberle said the new study implies Eocene alligators could withstand slightly cooler winters than their present-day counterparts, although data from captive alligators show they are heartier than other members of the crocodilian family and can survive short intervals of subfreezing temperatures by submerging themselves in the water.

In contrast, the existence of large land tortoises in the Eocene High Arctic is still somewhat puzzling, said Eberle, since today's large tortoises inhabit places like the Galapagos Islands where the cold-month average temperature is about 50 degrees F (10 degrees C.)

But during the late Pleistocene period some 10,000 to 50,000 years ago -- when air temperatures were comparable to those today -- large land tortoises were found as far north as present-day Pennsylvania and Illinois, Eberle said. This suggests their present range in the Americas does not represent their fullest geographic range as allowed by climate. Factors like hunting by early Native Americans and the past extent of glaciers probably are playing a role in today's distribution of giant tortoises, she said.

Eberle, who calls the new results "a deep time analogue" for today's rapidly warming Arctic region, said quantitative estimates of early Eocene climate conditions at high latitudes like Ellesmere Island are rare and often contradictory. Previous estimates of the early Eocene mean annual temperatures have ranged from 39 to 68 degrees F (4 to 20 degrees C), a temperature range equivalent to geographic ranges reaching from Canada to Florida.

There is high concern by scientists over a proposal to mine coal on Ellesmere Island at the ancient fossil site by WestStar Resources Inc. headquartered in Vancouver, British Columbia, Eberle said. "Sites like this are unique and extremely valuable resources that are of international importance, and shouldn't be allowed to disappear," she said. "Our concern is that coal mining activities could damage such sites and they will be lost forever."

Today Ellesmere Island is one of the coldest, driest environments on Earth and features tundra, permafrost, ice sheets, sparse vegetation and few mammals. The temperatures range from roughly minus 37 degrees F in winter (minus 38 C) to 48 degrees F (8 degrees C) in summer.

The new study foreshadows the impacts of continuing global warming on Arctic plants and animals, Eberle said. Temperatures in the Arctic are rising twice as fast as those at mid-latitudes as greenhouse gases build up in Earth's atmosphere, due primarily to human activities like fossil fuel burning and deforestation, according to climate scientists.

University of Colorado at Boulder

MOTHER OF ALL HUMANS LIVED 200,000 YEARS AGO

0 comentarios
The most robust statistical examination to date of our species' genetic links to "mitochondrial Eve" -- the maternal ancestor of all living humans -- confirms that she lived about 200,000 years ago. The Rice University study was based on a side-by-side comparison of 10 human genetic models that each aim to determine when Eve lived using a very different set of assumptions about the way humans migrated, expanded and spread across Earth.

The research is available online in the journal Theoretical Population Biology.

"Our findings underscore the importance of taking into account the random nature of population processes like growth and extinction," said study co-author Marek Kimmel, professor of statistics at Rice. "Classical, deterministic models, including several that have previously been applied to the dating of mitochondrial Eve, do not fully account for these random processes."

The quest to date mitochondrial Eve (mtEve) is an example of the way scientists probe the genetic past to learn more about mutation, selection and other genetic processes that play key roles in disease.

"This is why we are interested in patterns of genetic variability in general," Kimmel said. "They are very important for medicine."

For example, the way scientists attempt to date mtEve relies on modern genetic techniques. Genetic profiles of random blood donors are compared, and based upon the likenesses and differences between particular genes, scientists can assign a number that describes the degree to which any two donors are related to one another.

Using mitochondrial genomes to gauge relatedness is a way for geneticists to simplify the task of finding common ancestors that lived long ago. That is because the entire human genome contains more than 20,000 genes, and comparing the differences among so many genes for distant relatives is problematic, even with today's largest and fastest supercomputers.

But mitochondria -- the tiny organelles that serve as energy factories inside all human cells -- have their own genome. Besides containing 37 genes that rarely change, they contain a "hypervariable" region, which changes fast enough to provide a molecular clock calibrated to times comparable to the age of modern humanity. Because each person's mitochondrial genome is inherited from his or her mother, all mitochondrial lineages are maternal.

To infer mtEve's age, scientists must convert the measures of relatedness between random blood donors into a measure of time.

"You have to translate the differences between gene sequences into how they evolved in time," said co-author Krzysztof Cyran, vice head of the Institute of Informatics at Silesian University of Technology in Gliwice, Poland. "And how they evolved in time depends upon the model of evolution that you use. So, for instance, what is the rate of genetic mutation, and is that rate of change uniform in time? And what about the process of random loss of genetic variants, which we call genetic drift?"

Within each model, the answers to these questions take the form of coefficients -- numeric constants that are plugged into the equation that returns the answer for when mtEve lived.

Each model has its own assumptions, and each assumption has mathematical implications. To further complicate matters, some of the assumptions are not valid for human populations. For example, some models assume that population size never changes. That is not true for humans, whose population has grown exponentially for at least several thousand generations. Other models assume perfect mixing of genes, meaning that any two humans anywhere in the world have an equal chance of producing offspring.

Cyran said human genetic models have become more complex over the past couple of decades as theorists have tried to correct for invalid assumptions. But some of the corrections -- like adding branching processes that attempt to capture the dynamics of population growth in early human migrations -- are extremely complex. Which raises the question of whether less complex models might do equally well in capturing what's occurring.

"We wanted to see how sensitive the estimates were to the assumptions of the models," Kimmel said. "We found that all of the models that accounted for random population size -- such as different branching processes -- gave similar estimates. This is reassuring, because it shows that refining the assumptions of the model, beyond a certain point, may not be that important in the big picture."

Rice University

SCIENTISTS CLOSER TO FINDING WHAT CAUSES THE BIRTH OF A FAT CELL

0 comentarios
Just what causes the birth of a human fat cell is a mystery, but scientists using mathematics to tackle the question have come up with a few predictions about the proteins that influence this process.

The research is intended to increase understanding of how and why preadipocytes, or pre-fat cells, either lie dormant, copy themselves or turn into fat. But the findings eventually could lead to a way to freeze these early cells in their current state before they can ever become the basis of fat tissue, according to Ohio State University researchers.

Every human body needs fat to store and produce energy, but in excess, the tissue made up of fat cells begins to secrete molecules that send out complicated signals. This process can lead to inflammation and, in turn, to insulin resistance or diabetes, and contributes to the development of other diseases.

The scientists focused on three proteins that are known to have an impact on the fate of preadipocytes – one protein that influences inflammation; another that drives the creation of fat cells; and a third that is involved in the proliferation, or copying, of almost all cells in the body.

A series of differential equations determined how the complex interactions among these three proteins would likely affect what happens to pre-fat cells, including conditions most associated with quiescence, or keeping those preadipocytes from turning into fat.

A better appreciation of this process could help researchers more fully understand the causes of disorders associated with excess fat, including obesity and insulin resistance.

“A potential benefit of figuring out this process is to see how we could manipulate certain parameters to arrest cells in this quiescent region, and that could have an effect on obesity,” said Huseyin Coskun, a visiting assistant professor in the Department of Mathematics at Ohio State and lead author of the study.

“Obesity is certainly related to the types and amounts of foods people consume. But how the body responds to this can differ from one person to another, and could be related to some abnormalities in these protein interactions. The amount consumed may not be the only reason behind obesity. With this study, we started to understand how protein levels and complex molecular interactions in the body may influence the development of fat cells.”

The research is published in a recent issue of the Journal of Theoretical Biology.

Coskun, a mathematician, began this project by reading hundreds of journal articles about the biology behind the transition of preadipocytes into adipocytes, or fat cells. He identified 16 proteins that appeared to be the most active in the process.

He and the research group, a team of math and biology experts, narrowed that number to three high-impact proteins as a starting point. Coskun then designed differential equations based on the biological model that would show how the pre-fat cells behaved under a variety of conditions, depending on the proteins’ activity.

The three proteins are NF-kB, PPAR-gamma and cyclin D. NF-kB initiates inflammation in tissue. PPAR-gamma must be present for adipogenesis, or the creation of fat cells, to occur. And cyclin D is responsible for cell proliferation, or copying and growth, in almost all cells, including pre-fat cells and fat cells.

“The three target proteins of this initial model are the most commonly studied, but their mutual relationships in relation to the creation of fat cells are still not well-known, so we are putting their roles together to see how they contribute to fat cell determination for the first time, as far as we know, in the literature,” Coskun said.

The mathematical equations in which these three protein levels were manipulated resulted in a model that helped define the conditions under which pre-fat cells would remain dormant, start copying themselves or turn into fat cells. Two-parameter bifurcation curves are used for interpretation of model outcomes, which itself is a novel approach in terms of mathematical terminology.

The main parameters driving this model were two substances that affect the target proteins: a protein called IkB, which inhibits the inflammatory NF-kB protein, and the concentration of a chemical stimulant, called a mitogen, that stimulates production of cyclin D.

According to the model, if the level of IkB is high and the level of the cyclin D stimulant is low, the pre-fat cells remain dormant. The model then shows what is called a “curve of uncertainty,” which predicts the circumstances that are required for preadipocytes to either remain dormant or proliferate in their current state. The region of uncertainty then determines the conditions for coexistence of a pair of these three states: differentiation and quiescence, or proliferation and differentiation.

The researchers also conducted preliminary experiments to test the model’s outcomes by exposing mouse cells to TNF-alpha, a mitogen that stimulates cyclin D. They found that the concentrations of the proteins in those cells generally behaved as the model suggested they would. In addition, previous research reports of similar experiments also support the model’s outcomes, Coskun said.

He noted that more experiments are needed to further test the model, which also could be expanded to add more proteins to the equations.

Ohio State University

UF SCIENTISTS FIND GENETIC CLUES ABOUT PAIN INSENSITIVITY

0 comentarios
A baby who rarely cries is many parents’ idea of a “happy” baby. Ashlyn Blocker was that kind of baby.

She never cried at birth, when she was hungry, wet or teething. But when neither a severe diaper rash nor a cut on the surface of her eye caused the tiniest complaint, her parents, Tara and John Blocker, realized it wasn’t happiness that kept her quiet.

Ashlyn could not feel pain in a normal way.

Now, researchers at the University of Florida have pinpointed a major clue about her condition, called congenital insensitivity to pain. They identified two genetic mutations that affect how strongly pain signals are sent to the brain.

“This is a gene that, depending on how it is modified, has the ability to affect pain sensitivity to a large degree,” said Dr. Roland Staud, a pain expert and professor in the UF College of Medicine who led the study.

The findings shed light not just on the inability to feel pain, but also, at least potentially, on cases in which people feel unbearable or chronic pain. This knowledge ultimately could guide the development of novel and effective pain therapies.

The work appears in online and upcoming print editions of the European Journal of Pain.

Since 2004, Staud has collaborated with geneticists, neurologists, pediatricians and clinical psychologists to better understand Ashlyn’s condition. They evaluated the Blocker family, who live in Patterson, Ga., and 10 other individuals who feel pain normally.

“When we found out what gene it was, we were so excited,” Tara Blocker said. “It’s really nice to be able to say, ‘this is why.’ It might be little, but to us it’s huge. Finding out more about our daughter helps us take better care of her. ”

The gene in question, called SCN9A, contains the “message” to produce a molecule that acts as a battery to power pain-signaling nerve cells so they can fire impulses. Mutations that lead to overactivity of that molecule lead to severe pain, whereas those that cause the molecule not to function lead to the inability to feel pain.

“If you don’t have this gene it’s like a faint whisper in the wind,” Staud said. “Nothing much goes up the nerve, and you don’t feel anything.”

But Ashlyn, now 11, has a condition that is between the two extremes. Staud and colleagues found that the mutations decreased, but did not abolish, sensitivity to pain. Whereas Ashlyn cannot feel what is normally a painful touch or heat or cold, she can sense warmth and feel someone’s touch or tickle. But on rare occasions, in cases of very severe illness, she has said she hurts.

“This is an interesting finding — for many families just knowing that there is a physical cause for an abnormality, in this case a mutation that causes blunted ability to feel pain, can be helpful,” said Dr. Stephen G. Waxman, the Bridget Marie Flaherty professor of neurology at Yale University, and director of the Center for Neuroscience and Regeneration Research of the VA Connecticut Healthcare System. “Hopefully by studying patients with these mutations, we will more fully understand the gene’s role in pain signaling and in human pain disorders.”

Waxman, who was not involved in the study, pioneered research on the affected gene.

Insensitivity to pain is rare, and since the first reported case in 1932, only a few others have surfaced. Pain is a vital survival tool, because it alerts people to damage or potentially harmful situations. It is also a key element of emotional experiences such as empathy. Sickness and premature death occur in greater rates among people who are insensitive to pain.

Pain arises from both sensory and emotional stimuli, and involves various nerves and regions of the brain. Sensations or pain come as a result of contact with an object or other stimulus such as heat, when a signal is generated and transmitted to the brain. Sometimes, as in Ashlyn’s case, the signals don’t get through to the brain.

For Ashlyn, that has meant many injuries over the years. She has bitten the skin off her finger, chewed her bottom lip, gotten second-degree burns on her hand and broken her ankle in a bicycle accident without feeling any of it.

Her parents have had to watch her closely to make sure she doesn’t injure herself while doing the things she enjoys, such as swimming and running. They have also taught her how to look over her body for signs of injury.

While scientists potentially could manipulate genes to allow Ashlyn and others like her to feel pain more readily, they have to weigh the possibility that they might, in the process, set off other conditions such as epilepsy or hypersensitivity to pain, the researchers said. On the other end, the idea of creating genetic therapies to block pain raises questions about whether doctors should remove a person’s capacity to feel pain simply because he or she requests it.

For now, though, the UF researchers are focusing on identifying functional abnormalities associated with the genetic mutations, and ways in which the body compensates.

“It’s kind of an experiment of nature that we’re observing here,” Staud said.

University of Florida

Followers

Archive

 

Selected Science News. Copyright 2008 All Rights Reserved Revolution Two Church theme by Brian Gardner Converted into Blogger Template by Bloganol dot com