New research, conducted by Charles Wingo and his colleagues, at the University of Florida, Gainsville, suggests a link between the circadian rhythm and control of sodium (salt) levels in mice.
The hormone aldosterone regulates levels of sodium in the blood and thereby helps control blood pressure. Although it is known that aldosterone regulates sodium levels by controlling expression of the alpha-subunit of the epithelial sodium channel (alpha-ENaC) in the kidney, the molecular pathway by which aldosterone modulates alpha-ENaC levels has not been determined. In a previous study to address this issue, Wingo and colleagues found that aldosterone induced expression of the circadian clock gene Per1 in mouse cells, but the effects of this induction were not investigated. In this new study, they have revealed that the protein produced from the Per1 gene (Period 1) regulates expression of alpha-ENaC in the mouse kidney. Importantly, in the absence of Period 1, expression of alpha-ENaC in the mouse kidney was decreased and sodium loss in the urine was increased. Since expression from the Per1 gene seemed to follow a circadian pattern, the authors suggest that the circadian clock has a role in balancing sodium levels in the body.
TITLE: The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice
Source:
Karen Honey
Journal of Clinical Investigation
среда, 1 июня 2011 г.
Researchers Discover Missing Link In Cell Mitosis, The Role Of Protein In Controlling Cell Division Is Unveiled
A major discovery, led by researchers from The George Washington University Medical Center, promises to revolutionize the way scientists think about key aspects of cellular lifecycle and offers a new avenue for cancer researchers to explore in their quest to one day slow down the progression of cancer.
The discovery, reported in the article "Arpc 1b, a centrosomal protein, is both an activator and substrate of Aurora A," furthers the science world's understanding of what happens during the fundamental process of mitosis, when cells divide. The article was published in the current issue of The Journal of Cell Biology.
"This represents a crucial moment when the division of genetic material is still equally distributed. An even exchange is critical for stable genetic changes," said Rakesh Kumar, Ph.D., chair of the GW Department of Biochemistry and Molecular Biology. In mitosis, cells begin to divide and genetic material coalesces around separate poles to form new cells. If all goes well that material is evenly distributed and two genetically identical "daughter cells" are formed. If something goes awry, however, it can result in the cascading production of aberrant cells with unequal and less ordered DNA and possibly cancer.
Lead authors Poonam R. Molli, Ph.D., ex-postdoctoral fellow, and Da-Qiang Li, M.D., assistant research professor, from GW's Department of Biochemistry and Molecular Biology, have identified a protein, Arpc 1b, that serves as both an activator as well as a substrate for Aurora A, an enzyme which plays a central role in cellular reproduction in normal cells but is overexpressed in several cancers. This represents perhaps the earliest step in mitosis and serves as the missing link regarding the role this protein plays in starting the cell cycle and what keeps the process in balance. The authors discovered that Arpc1b also exists as a stand alone protein and believe that it might also play an independent role outside its established contribution to actin machinery.
More than just an observation of how cells divide, this discovery also offers a potential target for pharmaceutical therapy. Both Aurora A and Arpc1b are over-expressed in breast cancers. Pharmaceutical inhibitors targeting Aurora A are currently available and thus, could be combined with other future targeting strategies. The researchers discovered that an over-expression of Arpc1b promotes tumorigenic properties of breast cancer cells. Scientists believe that if they can someday find a means of suppressing the activity of Arpc 1b in cancer cell, the balance could be restored to this dynamic yet tightly regulated biological event.
"This discovery is the result of persistence and the commitment to scientific breakthrough," said Dr. Kumar. "Asking a question and staying involved until you find the answer to close the loop is critical in scientific discovery." In this case the earliest piece of data used here was obtained in 2001.
About The George Washington University Medical Center
The George Washington University Medical Center is an internationally recognized interdisciplinary academic health center that has consistently provided high-quality medical care in the Washington, D.C. metropolitan area since 1824. The Medical Center comprises the School of Medicine and Health Sciences, the 11th oldest medical school in the country; the School of Public Health and Health Services, the only such school in the nation's capital; GW Hospital, jointly owned and operated by a partnership between The George Washington University and a subsidiary of Universal Health Services, Inc.; and The GW Medical Faculty Associates, an independent medical practice with nearly 550 physicians in 47 clinical specialties.
Source: George Washington University Medical Center
The discovery, reported in the article "Arpc 1b, a centrosomal protein, is both an activator and substrate of Aurora A," furthers the science world's understanding of what happens during the fundamental process of mitosis, when cells divide. The article was published in the current issue of The Journal of Cell Biology.
"This represents a crucial moment when the division of genetic material is still equally distributed. An even exchange is critical for stable genetic changes," said Rakesh Kumar, Ph.D., chair of the GW Department of Biochemistry and Molecular Biology. In mitosis, cells begin to divide and genetic material coalesces around separate poles to form new cells. If all goes well that material is evenly distributed and two genetically identical "daughter cells" are formed. If something goes awry, however, it can result in the cascading production of aberrant cells with unequal and less ordered DNA and possibly cancer.
Lead authors Poonam R. Molli, Ph.D., ex-postdoctoral fellow, and Da-Qiang Li, M.D., assistant research professor, from GW's Department of Biochemistry and Molecular Biology, have identified a protein, Arpc 1b, that serves as both an activator as well as a substrate for Aurora A, an enzyme which plays a central role in cellular reproduction in normal cells but is overexpressed in several cancers. This represents perhaps the earliest step in mitosis and serves as the missing link regarding the role this protein plays in starting the cell cycle and what keeps the process in balance. The authors discovered that Arpc1b also exists as a stand alone protein and believe that it might also play an independent role outside its established contribution to actin machinery.
More than just an observation of how cells divide, this discovery also offers a potential target for pharmaceutical therapy. Both Aurora A and Arpc1b are over-expressed in breast cancers. Pharmaceutical inhibitors targeting Aurora A are currently available and thus, could be combined with other future targeting strategies. The researchers discovered that an over-expression of Arpc1b promotes tumorigenic properties of breast cancer cells. Scientists believe that if they can someday find a means of suppressing the activity of Arpc 1b in cancer cell, the balance could be restored to this dynamic yet tightly regulated biological event.
"This discovery is the result of persistence and the commitment to scientific breakthrough," said Dr. Kumar. "Asking a question and staying involved until you find the answer to close the loop is critical in scientific discovery." In this case the earliest piece of data used here was obtained in 2001.
About The George Washington University Medical Center
The George Washington University Medical Center is an internationally recognized interdisciplinary academic health center that has consistently provided high-quality medical care in the Washington, D.C. metropolitan area since 1824. The Medical Center comprises the School of Medicine and Health Sciences, the 11th oldest medical school in the country; the School of Public Health and Health Services, the only such school in the nation's capital; GW Hospital, jointly owned and operated by a partnership between The George Washington University and a subsidiary of Universal Health Services, Inc.; and The GW Medical Faculty Associates, an independent medical practice with nearly 550 physicians in 47 clinical specialties.
Source: George Washington University Medical Center
Genes From Fireflies And Jellyfish Shed Light On Possible Causes Of Infertility And Autoimmune Diseases In Humans
Genes taken from fireflies and jellyfish are literally shedding light on possible causes of infertility and autoimmune diseases in humans.
Scientists are using the luminescent and florescent genes to illuminate cells that produce a hormone linked to conditions, which include rheumatoid arthritis and lupus.
The technique will help scientists track the production of the hormone prolactin, which is crucial in ensuring supplies of breast milk in nursing mothers but can be overproduced by some pituitary tumours, causing infertility.
Prolactin has been linked to more than 300 biological functions. It is believed to play a role in autoimmune diseases, such as lupus and rheumatoid arthritis, as well as in the inflammation of cells and tissues.
Scientists from the Universities of Edinburgh, Manchester and Liverpool harnessed firefly and jellyfish genes, which enable these creatures to emit light, and used them to create a chemical reaction to light up cells expressing prolactin in rats.
The technique means that scientists can identify when and where prolactin is expressed to look at how the hormone works in real time.
Sabrina Semprini, whose study is published in the journal Molecular Endocrinology, said: "The lighting up of cells expressing this hormone will help us to understand its role within the body and could help research looking for treatments for conditions in which prolactin is involved."
The research, funded by the Wellcome Trust, identified cells producing prolactin throughout the body. This included the pituitary gland, the thymus - an organ in the chest which helps protect against autoimmunity - the spleen and inflammatory cells in the abdominal cavity.
Source:
Tara Womersley
University of Edinburgh
Scientists are using the luminescent and florescent genes to illuminate cells that produce a hormone linked to conditions, which include rheumatoid arthritis and lupus.
The technique will help scientists track the production of the hormone prolactin, which is crucial in ensuring supplies of breast milk in nursing mothers but can be overproduced by some pituitary tumours, causing infertility.
Prolactin has been linked to more than 300 biological functions. It is believed to play a role in autoimmune diseases, such as lupus and rheumatoid arthritis, as well as in the inflammation of cells and tissues.
Scientists from the Universities of Edinburgh, Manchester and Liverpool harnessed firefly and jellyfish genes, which enable these creatures to emit light, and used them to create a chemical reaction to light up cells expressing prolactin in rats.
The technique means that scientists can identify when and where prolactin is expressed to look at how the hormone works in real time.
Sabrina Semprini, whose study is published in the journal Molecular Endocrinology, said: "The lighting up of cells expressing this hormone will help us to understand its role within the body and could help research looking for treatments for conditions in which prolactin is involved."
The research, funded by the Wellcome Trust, identified cells producing prolactin throughout the body. This included the pituitary gland, the thymus - an organ in the chest which helps protect against autoimmunity - the spleen and inflammatory cells in the abdominal cavity.
Source:
Tara Womersley
University of Edinburgh
Pregnant, Constipated And Bloated? Fly Faeces May Tell You Why
Clues about how the human gut helps regulate our appetite have come from a most unusual source - fruit fly faeces. Scientists at the University of Cambridge are using the fruit fly to help understand aspects of human metabolism, including why pregnant women suffer from bloating and constipation, and even the link between a low calorie diet and longevity.
Although scientists have known for some time that there are as many as 500 million nerve cells in our gut, the sheer complexity that this presents means that little is known about the different types of nerve cell and their functions.
Now, researchers led by Dr Irene Miguel-Aliaga, with funding from the Wellcome Trust and the Biotechnology and Biological Sciences Research Council, have used the fruit fly, Drosophila melanogaster, to investigate the function of these intestinal neurons. The fly has simpler versions of our nervous and digestive systems, which lend it to genetic manipulation. Their findings are published in the journal Cell Metabolism.
"We reasoned that what comes out of the gut may be able to tell us about what is going on inside," explains Dr Miguel-Aliaga. "So, we devised a method to extract information about several metabolic features from the flies' faecal deposits - which are actually rather pretty and don't smell bad. Then we turned specific neurons on and off and examined what came out."
Dr Miguel-Aliaga and colleagues found that these intestinal neurons have very important and specialised functions, such as regulating appetite or adjusting intestinal water balance during reproduction.
Female flies in their reproductive stage get constipated - their gut emptying rate is reduced even though they are eating more food; at the same time, they retain more water and the contents of their intestines become more concentrated. The researchers showed that these intestinal changes are triggered by the sex peptide, a hormone that males inject into the female during copulation, which activates of a small group of gut neurons. This shares the same function as the sex hormones found in humans, such as progesterone, oxytocin and oestrogen.
"Humans and fruit flies reproduce in very different ways, yet the associated symptoms of constipation and bloating and their cause - a reproductive hormone - are the same," explains Dr Miguel-Aliaga. "This suggests that this mechanism has been conserved through evolution. These intestinal changes may provide a benefit at a time of high nutritional demand by maximizing nutrient absorption."
The research also provides tantalising clues about the link between calorie intake and longevity. Intestinal changes which help maximize nutrient absorption would likely be active all the time, as they would provide a selective advantage when food is scarce. However, in flies - and possibly in humans - this may come at a cost: a shorter lifespan.
It has been known for some time that when female flies mate and receive the sex peptide, this shortens their lifespan; however, this is not caused entirely by their increased food intake or because they are laying many eggs, the two most obvious effects of this sex peptide. The explanation, argue the researchers, may lie in the intestinal changes triggered by the sex peptide that lead to constipation and water retention.
"A mechanism that maximises nutrient absorption by slowing the passage of food through the intestine is fine when food is scarce or during reproduction," says Dr Miguel-Aliaga, "but when we are eating a normal diet, constipation may lead to the build up of waste products produced during internal metabolism. Similarly, it could lead to changes in the composition of the gut bacteria, which are essential to regulating metabolism.
"Our research suggests that in addition to paying attention to what we eat, which has been the focus of longevity research, we may also have to consider what our body does with the food and what goes on in our guts."
Source:
Craig Brierley
Wellcome Trust
Although scientists have known for some time that there are as many as 500 million nerve cells in our gut, the sheer complexity that this presents means that little is known about the different types of nerve cell and their functions.
Now, researchers led by Dr Irene Miguel-Aliaga, with funding from the Wellcome Trust and the Biotechnology and Biological Sciences Research Council, have used the fruit fly, Drosophila melanogaster, to investigate the function of these intestinal neurons. The fly has simpler versions of our nervous and digestive systems, which lend it to genetic manipulation. Their findings are published in the journal Cell Metabolism.
"We reasoned that what comes out of the gut may be able to tell us about what is going on inside," explains Dr Miguel-Aliaga. "So, we devised a method to extract information about several metabolic features from the flies' faecal deposits - which are actually rather pretty and don't smell bad. Then we turned specific neurons on and off and examined what came out."
Dr Miguel-Aliaga and colleagues found that these intestinal neurons have very important and specialised functions, such as regulating appetite or adjusting intestinal water balance during reproduction.
Female flies in their reproductive stage get constipated - their gut emptying rate is reduced even though they are eating more food; at the same time, they retain more water and the contents of their intestines become more concentrated. The researchers showed that these intestinal changes are triggered by the sex peptide, a hormone that males inject into the female during copulation, which activates of a small group of gut neurons. This shares the same function as the sex hormones found in humans, such as progesterone, oxytocin and oestrogen.
"Humans and fruit flies reproduce in very different ways, yet the associated symptoms of constipation and bloating and their cause - a reproductive hormone - are the same," explains Dr Miguel-Aliaga. "This suggests that this mechanism has been conserved through evolution. These intestinal changes may provide a benefit at a time of high nutritional demand by maximizing nutrient absorption."
The research also provides tantalising clues about the link between calorie intake and longevity. Intestinal changes which help maximize nutrient absorption would likely be active all the time, as they would provide a selective advantage when food is scarce. However, in flies - and possibly in humans - this may come at a cost: a shorter lifespan.
It has been known for some time that when female flies mate and receive the sex peptide, this shortens their lifespan; however, this is not caused entirely by their increased food intake or because they are laying many eggs, the two most obvious effects of this sex peptide. The explanation, argue the researchers, may lie in the intestinal changes triggered by the sex peptide that lead to constipation and water retention.
"A mechanism that maximises nutrient absorption by slowing the passage of food through the intestine is fine when food is scarce or during reproduction," says Dr Miguel-Aliaga, "but when we are eating a normal diet, constipation may lead to the build up of waste products produced during internal metabolism. Similarly, it could lead to changes in the composition of the gut bacteria, which are essential to regulating metabolism.
"Our research suggests that in addition to paying attention to what we eat, which has been the focus of longevity research, we may also have to consider what our body does with the food and what goes on in our guts."
Source:
Craig Brierley
Wellcome Trust
New Clues To Mammalian Evolution Provided By Mobile DNA Elements In Woolly Mammoth Genome
The woolly mammoth died out several thousand years ago, but the genetic material they left behind is yielding new clues about the evolution of mammals. In a study published online in Genome Research, scientists have analyzed the mammoth genome looking for mobile DNA elements, revealing new insights into how some of these elements arose in mammals and shaped the genome of an animal headed for extinction.
Interspersed repeats, also known as transposable elements, are DNA sequences that can "jump" around the genome, causing mutations in the host and contributing to expansion of the genome. Interspersed repeats account for a significant fraction of mammalian genomes, and some of these elements are still actively mobile. In humans, interspersed repeats account for approximately 44% of the entire genome sequence. Even more extreme is the opossum genome, where more than half of the sequence is composed of repetitive elements.
Scientists recently sequenced the woolly mammoth genome, using DNA samples obtained from preserved specimens. Dr. Stephan Schuster and his research group at Penn State University, who were involved in the sequencing and analysis of the mammoth genome, are now looking deeper into the sequence for interspersed repeats. The mammoth genome is an excellent candidate for comparative analysis of interspersed repeats in mammals, as it had a remarkably large genome of approximately 4.7 billion bases, 1.5 times larger than the human genome. Using the mammoth genome sequence and sequences of other mammals for comparison, Schuster's group found that the mammoth genome contained the largest proportion of interspersed repeats of any other mammal studied. In fact, a single class of elements, known as the BovB long interspersed repeat, accounted for nearly 12% of the mammoth genome alone.
Dr. Fangqing Zhao, a postdoctoral researcher in Schuster's group and primary author of the work, emphasized that the BovB family of repeats is particularly interesting, because while this family has been identified in other mammalian genomes, such as ruminants, snakes, opossum, and now the mammoth, its distribution in the mammalian lineage is inconsistent. Zhao explained that this finding in mammoth further supports the hypothesis that BovB may have been acquired "horizontally," meaning that vertebrate genomes attained the element from another organism, rather than inherited from ancestors.
Many species within the Afrotheria group of mammals, which includes the woolly mammoth, are at high risk for extinction or are already extinct. "Further analyses examining if the genomes of extinct and endangered Afrotherians contain more repetitive elements than non-endangered mammals may elucidate whether there is an interplay between repetitive elements and extinction," Zhao noted, underscoring the need to study genomes of species on the brink of extinction.
Notes:
Scientists from Penn State University (University Park, PA) contributed to this study. Stephan C. Schuster, Ph.D. is supported by the Gordon and Betty Moore Foundation.
About the article:
The manuscript is published online ahead of print on June 9, 2009. Its full citation is as follows: Zhao F, Qi J, and Schuster SC. Tracking the past: Interspersed repeats in an extinct Afrotherian mammal, Mammuthus primigenius. Genome Res doi:10.1101/gr.091363.109.
Source:
Peggy Calicchia
Cold Spring Harbor Laboratory
Interspersed repeats, also known as transposable elements, are DNA sequences that can "jump" around the genome, causing mutations in the host and contributing to expansion of the genome. Interspersed repeats account for a significant fraction of mammalian genomes, and some of these elements are still actively mobile. In humans, interspersed repeats account for approximately 44% of the entire genome sequence. Even more extreme is the opossum genome, where more than half of the sequence is composed of repetitive elements.
Scientists recently sequenced the woolly mammoth genome, using DNA samples obtained from preserved specimens. Dr. Stephan Schuster and his research group at Penn State University, who were involved in the sequencing and analysis of the mammoth genome, are now looking deeper into the sequence for interspersed repeats. The mammoth genome is an excellent candidate for comparative analysis of interspersed repeats in mammals, as it had a remarkably large genome of approximately 4.7 billion bases, 1.5 times larger than the human genome. Using the mammoth genome sequence and sequences of other mammals for comparison, Schuster's group found that the mammoth genome contained the largest proportion of interspersed repeats of any other mammal studied. In fact, a single class of elements, known as the BovB long interspersed repeat, accounted for nearly 12% of the mammoth genome alone.
Dr. Fangqing Zhao, a postdoctoral researcher in Schuster's group and primary author of the work, emphasized that the BovB family of repeats is particularly interesting, because while this family has been identified in other mammalian genomes, such as ruminants, snakes, opossum, and now the mammoth, its distribution in the mammalian lineage is inconsistent. Zhao explained that this finding in mammoth further supports the hypothesis that BovB may have been acquired "horizontally," meaning that vertebrate genomes attained the element from another organism, rather than inherited from ancestors.
Many species within the Afrotheria group of mammals, which includes the woolly mammoth, are at high risk for extinction or are already extinct. "Further analyses examining if the genomes of extinct and endangered Afrotherians contain more repetitive elements than non-endangered mammals may elucidate whether there is an interplay between repetitive elements and extinction," Zhao noted, underscoring the need to study genomes of species on the brink of extinction.
Notes:
Scientists from Penn State University (University Park, PA) contributed to this study. Stephan C. Schuster, Ph.D. is supported by the Gordon and Betty Moore Foundation.
About the article:
The manuscript is published online ahead of print on June 9, 2009. Its full citation is as follows: Zhao F, Qi J, and Schuster SC. Tracking the past: Interspersed repeats in an extinct Afrotherian mammal, Mammuthus primigenius. Genome Res doi:10.1101/gr.091363.109.
Source:
Peggy Calicchia
Cold Spring Harbor Laboratory
Reptiles' Muscles Move Lungs For Sneaky Maneuvers In Water
Without a ripple in the water, alligators dive, surface or roll sideways, even though they lack flippers or fins. University of Utah biologists discovered gators maneuver silently by using their diaphragm, pelvic, abdominal and rib muscles to shift their lungs like internal floatation devices: toward the tail when they dive, toward the head when they surface and sideways when they roll.
"It allows them to navigate a watery environment without creating a lot of disturbance," says doctoral student T.J. Uriona. "This is probably really important while they are trying to sneak up on an animal but don't want to create ripples."
The discovery in American alligators suggests "special muscles that manipulate the position of the lungs - and thus the center of buoyancy - may be an underappreciated but important means for other aquatic animals to maneuver in water without actively swimming," says C.G. Farmer, an assistant professor of biology.
Those animals include crocodiles, African clawed frogs, some salamanders, turtles and manatees, she adds, noting that the use of muscles to move the lungs may be "incredibly important or you would not see it evolve repeatedly."
The study by Uriona and Farmer will be published in the April 2008 issue of The Journal of Experimental Biology, which is set for online publication Friday, March 14.
The researchers found that alligators are somewhat like pilots using controls to adjust an aircraft's pitch and roll, except the reptiles' controls are muscles that help them shift their lungs backward to dive, forward to surface or sideways to roll.
Farmer says the new study asked how gators "manage to maneuver so gracefully without the fins and flippers used by fish, seals and other adept swimmers?"
"The secret to their aquatic agility lies in the use of several muscles, such as the diaphragmatic muscle, to shift the position of their lungs. The gases in the lungs buoy up the animal, but if shifted forward and backward cause the animal to pivot in a seesaw motion. When the animals displace gases to the right or left side of the body, they roll."
Uriona says that during the Triassic Period, which began 250 million years ago, the crocodilian ancestors of alligators were cat-sized animals that lived only on land.
"Until now, it was believed the diaphragmatic muscle evolved to help them breathe and run at the same time," he says. "Showing they are actually using it to move around in water gives an alternative explanation for why the muscle evolved."
It also suggests the muscle didn't evolve until after crocodilians took to the water during the Cretaceous Period, which began 145 million years ago. During that time alligators' ancestors also evolved a flattened skull, shorter limbs and a big tail.
Studying the Crocodile Rock
The study involved five, 2-year-old American alligators (Alligator mississippiensis) from Louisiana's Rockefeller Wildlife Refuge near Grand Chenier. The gators were only 15 inches to 20 inches long, compared with adults that can reach 15 feet.
Electrodes were implanted on five sets of muscles so their activity could be monitored while the alligators maneuvered in 100-gallon fish tanks. One set of muscles played no role in moving the lungs to help the gators dive and maneuver, but four did:
-- The diaphragmaticus, which plays a role in breathing like the diaphragm that separates the chest cavity from the abdominal cavity in humans and other mammals. But in gators, it runs parallel to the belly and encases the stomach and intestines. When an alligator inhales, the diaphragmaticus pulls the liver back toward the pelvis and tail. The liver is attached to the lungs, so when the liver is pulled back, it expands the lungs.
-- The ischiopubis muscles, with one on each side of an alligator's pelvis. Each ischiopubis muscle connects a pubis bone to an ischium bone. Unlike humans, who have their pelvic bones fused together, the pubes and ischia are not fused in gators, so the ischiopubis muscles allow gators to puff out their bellies, helping pull the liver toward the tail so the lungs inflate when the animal inhales.
-- The rectus abdominis muscles, which Uriona describes as the gator equivalent of "six packs," "abs" or abdominal muscles. In most animals, these muscles help maintain posture. In crocodilians, these muscles encase the belly ribs, helping push the guts upward to force air from the lungs when the animals exhale.
-- The internal intercostals, which are muscles between an alligator's ribs - the kind of muscles people eat when they order pork or beef ribs. There are two groups of chest rib muscles. One group helps the rib cage contract and pushes air out of the lungs when gators exhale; the other helps the rib cage expand during inhalation.
Of the muscles listed above, some are used for inhaling and some for exhaling. Yet the study found all four muscle types work together to help an alligator shift its lungs so it can rock downward to dive or roll side-to-side. The tail also helps gators roll.
"The muscles are on when they are diving, and the muscles shut off when they start returning to the surface," Uriona says.
The Alligators' Burden
As part of the study, Uriona created small weights - equal to only 2.5 percent of each gator's body weight - by wrapping buckshot pellets in duct tape.
When a weight was duct-taped to an alligator's snout, it helped the alligator dive. As a result, the electrical recordings showed that there was reduced activity of muscles needed to help diving - muscles that pull the lungs backward to help lift the tail.
When a weight was duct-taped at the base of a gator's tail, it made diving more difficult, and the biologists recorded increased activity of muscles needed to pull the lungs back to assist diving.
"We showed with the weights that they can adjust how much they activate those muscles to meet whatever conditions require," Uriona says. In other words, the gators exert fine control over the muscles used to shift their lungs for aquatic maneuvers.
Gators on an Evolutionary Roll
Until now, researchers assumed alligators' land-dwelling ancestors developed the diaphragmaticus muscle to help them breathe while running.
"It may be that instead of these muscles arising for breathing, they arose for moving around in the water and later were co-opted for breathing," Uriona says.
He says natural selection would favor the development of muscles to move the lungs for quiet maneuvers in water because animals with such ability can easily "move around in the water, either trying to sneak up and eat something, or avoid being eaten."
Uriona says the diaphragmaticus likely began as part of the rectus abdominis muscle and evolved into a separate muscle.
If the diaphragm-like muscle evolved to help breathing, two steps were required. First, the diaphragmaticus' connection to the breastbone had to be replaced by a connection to the liver. Second, separate nerve circuits had to evolve to control the diaphragmaticus and "abs" since one is used to inhale and the other to exhale.
If, instead, the diaphragmaticus first evolved to help ancient crocs maneuver in water, only the first step would have been required. When the diaphragm-like muscle and other muscles later evolved to assist breathing, then the second step was needed.
Uriona and Farmer say it is simpler evolutionarily for one step to occur at a time, making it more logical that the diaphragm evolved first when early crocodilians took to the water, and began to play a role in breathing only later.
To turn or otherwise maneuver in water or air, animals must generate lift or drag - and that requires speed, Farmer says. So the ability to move the lungs to maneuver "is probably key for slow swimmers," she adds. "This mechanism allows these animals to manipulate their posture without generating lift or drag - without any swimming movement like the flick of a tail or swish of a fin."
The study was funded by the National Science Foundation, the University of Utah and a private donor, Sharon Meyers of California.
University of Utah
"It allows them to navigate a watery environment without creating a lot of disturbance," says doctoral student T.J. Uriona. "This is probably really important while they are trying to sneak up on an animal but don't want to create ripples."
The discovery in American alligators suggests "special muscles that manipulate the position of the lungs - and thus the center of buoyancy - may be an underappreciated but important means for other aquatic animals to maneuver in water without actively swimming," says C.G. Farmer, an assistant professor of biology.
Those animals include crocodiles, African clawed frogs, some salamanders, turtles and manatees, she adds, noting that the use of muscles to move the lungs may be "incredibly important or you would not see it evolve repeatedly."
The study by Uriona and Farmer will be published in the April 2008 issue of The Journal of Experimental Biology, which is set for online publication Friday, March 14.
The researchers found that alligators are somewhat like pilots using controls to adjust an aircraft's pitch and roll, except the reptiles' controls are muscles that help them shift their lungs backward to dive, forward to surface or sideways to roll.
Farmer says the new study asked how gators "manage to maneuver so gracefully without the fins and flippers used by fish, seals and other adept swimmers?"
"The secret to their aquatic agility lies in the use of several muscles, such as the diaphragmatic muscle, to shift the position of their lungs. The gases in the lungs buoy up the animal, but if shifted forward and backward cause the animal to pivot in a seesaw motion. When the animals displace gases to the right or left side of the body, they roll."
Uriona says that during the Triassic Period, which began 250 million years ago, the crocodilian ancestors of alligators were cat-sized animals that lived only on land.
"Until now, it was believed the diaphragmatic muscle evolved to help them breathe and run at the same time," he says. "Showing they are actually using it to move around in water gives an alternative explanation for why the muscle evolved."
It also suggests the muscle didn't evolve until after crocodilians took to the water during the Cretaceous Period, which began 145 million years ago. During that time alligators' ancestors also evolved a flattened skull, shorter limbs and a big tail.
Studying the Crocodile Rock
The study involved five, 2-year-old American alligators (Alligator mississippiensis) from Louisiana's Rockefeller Wildlife Refuge near Grand Chenier. The gators were only 15 inches to 20 inches long, compared with adults that can reach 15 feet.
Electrodes were implanted on five sets of muscles so their activity could be monitored while the alligators maneuvered in 100-gallon fish tanks. One set of muscles played no role in moving the lungs to help the gators dive and maneuver, but four did:
-- The diaphragmaticus, which plays a role in breathing like the diaphragm that separates the chest cavity from the abdominal cavity in humans and other mammals. But in gators, it runs parallel to the belly and encases the stomach and intestines. When an alligator inhales, the diaphragmaticus pulls the liver back toward the pelvis and tail. The liver is attached to the lungs, so when the liver is pulled back, it expands the lungs.
-- The ischiopubis muscles, with one on each side of an alligator's pelvis. Each ischiopubis muscle connects a pubis bone to an ischium bone. Unlike humans, who have their pelvic bones fused together, the pubes and ischia are not fused in gators, so the ischiopubis muscles allow gators to puff out their bellies, helping pull the liver toward the tail so the lungs inflate when the animal inhales.
-- The rectus abdominis muscles, which Uriona describes as the gator equivalent of "six packs," "abs" or abdominal muscles. In most animals, these muscles help maintain posture. In crocodilians, these muscles encase the belly ribs, helping push the guts upward to force air from the lungs when the animals exhale.
-- The internal intercostals, which are muscles between an alligator's ribs - the kind of muscles people eat when they order pork or beef ribs. There are two groups of chest rib muscles. One group helps the rib cage contract and pushes air out of the lungs when gators exhale; the other helps the rib cage expand during inhalation.
Of the muscles listed above, some are used for inhaling and some for exhaling. Yet the study found all four muscle types work together to help an alligator shift its lungs so it can rock downward to dive or roll side-to-side. The tail also helps gators roll.
"The muscles are on when they are diving, and the muscles shut off when they start returning to the surface," Uriona says.
The Alligators' Burden
As part of the study, Uriona created small weights - equal to only 2.5 percent of each gator's body weight - by wrapping buckshot pellets in duct tape.
When a weight was duct-taped to an alligator's snout, it helped the alligator dive. As a result, the electrical recordings showed that there was reduced activity of muscles needed to help diving - muscles that pull the lungs backward to help lift the tail.
When a weight was duct-taped at the base of a gator's tail, it made diving more difficult, and the biologists recorded increased activity of muscles needed to pull the lungs back to assist diving.
"We showed with the weights that they can adjust how much they activate those muscles to meet whatever conditions require," Uriona says. In other words, the gators exert fine control over the muscles used to shift their lungs for aquatic maneuvers.
Gators on an Evolutionary Roll
Until now, researchers assumed alligators' land-dwelling ancestors developed the diaphragmaticus muscle to help them breathe while running.
"It may be that instead of these muscles arising for breathing, they arose for moving around in the water and later were co-opted for breathing," Uriona says.
He says natural selection would favor the development of muscles to move the lungs for quiet maneuvers in water because animals with such ability can easily "move around in the water, either trying to sneak up and eat something, or avoid being eaten."
Uriona says the diaphragmaticus likely began as part of the rectus abdominis muscle and evolved into a separate muscle.
If the diaphragm-like muscle evolved to help breathing, two steps were required. First, the diaphragmaticus' connection to the breastbone had to be replaced by a connection to the liver. Second, separate nerve circuits had to evolve to control the diaphragmaticus and "abs" since one is used to inhale and the other to exhale.
If, instead, the diaphragmaticus first evolved to help ancient crocs maneuver in water, only the first step would have been required. When the diaphragm-like muscle and other muscles later evolved to assist breathing, then the second step was needed.
Uriona and Farmer say it is simpler evolutionarily for one step to occur at a time, making it more logical that the diaphragm evolved first when early crocodilians took to the water, and began to play a role in breathing only later.
To turn or otherwise maneuver in water or air, animals must generate lift or drag - and that requires speed, Farmer says. So the ability to move the lungs to maneuver "is probably key for slow swimmers," she adds. "This mechanism allows these animals to manipulate their posture without generating lift or drag - without any swimming movement like the flick of a tail or swish of a fin."
The study was funded by the National Science Foundation, the University of Utah and a private donor, Sharon Meyers of California.
University of Utah
Generating RNA Molecules In Water, Just Like Old Times
A key question in the origin of biological molecules like RNA and DNA is how they first came together billions of years ago from simple precursors. Now, in a study appearing in this week's JBC, researchers in Italy have reconstructed one of the earliest evolutionary steps yet: generating long chains of RNA from individual subunits using nothing but warm water.
Many researchers believe that RNA was one of the first biological molecules present, before DNA and proteins; however, there has been little success in recreating the formation on RNA from simple "prebiotic" molecules that likely were present on primordial earth billions of years ago.
Now, Ernesto Di Mauro and colleagues found that ancient molecules called cyclic nucleotides can merge together in water and form polymers over 100 nucleotides long in water ranging from 40-90 °C - similar to water temperatures on ancient Earth.
Cyclic nucleotides like cyclic-AMP are very similar to the nucleotides that make up individual pieces of DNA or RNA (A, T, G and C), except that they form an extra chemical bond and assume a ring-shaped structure. That extra bond makes cyclic nucleotides more reactive, though, and thus they were able to join together into long chains at a decent rate (about 200 hours to reach 100 nucleotides long).
This finding is exciting as cyclic nucleotides themselves can be easily formed from simple chemicals like formamide, thus making them plausible prebiotic compounds present during primordial times. Thus, this study may be revealing how the first bits of genetic information were created.
From the JBC article: Generation of Long RNA Chains in Water" by Giovanna Costanzo, Samanta Pino, Fabiana Ciciriello and Ernesto Di Mauro
Article link: jbc/content/early/2009/10/02/jbc.M109.041905
Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology
Many researchers believe that RNA was one of the first biological molecules present, before DNA and proteins; however, there has been little success in recreating the formation on RNA from simple "prebiotic" molecules that likely were present on primordial earth billions of years ago.
Now, Ernesto Di Mauro and colleagues found that ancient molecules called cyclic nucleotides can merge together in water and form polymers over 100 nucleotides long in water ranging from 40-90 °C - similar to water temperatures on ancient Earth.
Cyclic nucleotides like cyclic-AMP are very similar to the nucleotides that make up individual pieces of DNA or RNA (A, T, G and C), except that they form an extra chemical bond and assume a ring-shaped structure. That extra bond makes cyclic nucleotides more reactive, though, and thus they were able to join together into long chains at a decent rate (about 200 hours to reach 100 nucleotides long).
This finding is exciting as cyclic nucleotides themselves can be easily formed from simple chemicals like formamide, thus making them plausible prebiotic compounds present during primordial times. Thus, this study may be revealing how the first bits of genetic information were created.
From the JBC article: Generation of Long RNA Chains in Water" by Giovanna Costanzo, Samanta Pino, Fabiana Ciciriello and Ernesto Di Mauro
Article link: jbc/content/early/2009/10/02/jbc.M109.041905
Source: Nick Zagorski
American Society for Biochemistry and Molecular Biology
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