Synthetic lethality: A new way to kill cancer cells

Ovarian and breast cancer treatments being developed that mix a protein inhibitor and traditional anticancer drugs are showing signs of success, according to a new review for Faculty of 1000 Biology Reports.

Susan Bates and Christina Annunziata looked at several recent papers on this form of treatment, which takes advantage of the synthetic lethality of BRCA (breast cancer susceptibility genes) and poly-ADP ribose polymerase (PARP) proteins to attack cancerous cells whilst sparing healthy ones.

BRCA and PARP are two key players in DNA repair and have different but complementary functions in the cell. Loss of the BRCA protein still allows the cell to survive but greatly increases its chances of becoming cancerous through the accumulation of mutations. The loss of both proteins, however, kills the cell in a process called synthetic lethality.

Researchers, by using drugs to block the activity of PARP in cells missing BRCA, such as those found in certain breast and ovarian cancers, can help spare healthy, non-cancerous cells because they have functional BRCA and are not affected by the loss of PARP. Thus, only cancer cells without functional BRCA protein are killed by drugs that inhibit PARP.

Recent clinical trials have shown that cancers caused by mutations that knock out BRCA activity can be controlled by blocking PARP activity with specific drugs. Patients were treated with traditional anticancer drugs alone or in combination with one of two new PARP inhibitors, olaparib or BSI-201.

Bates notes that patients on combination therapy had improved "[disease] progression-free survival, and overall survival" as compared to patients treated with traditional drugs alone.

Bates is optimistic about the promise of combining PARP inhibitors with existing cancer drugs. She says that the results of these clinical trials "have provided proof of principle in achieving synthetic lethality" with PARP-inhibiting drugs and that treatments combining novel PARP inhibitors with traditional chemotherapeutic drugs have the potential to vanquish BRCA-associated breast and ovarian cancers.

Source : Faculty of 1000: Biology and Medicine

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New dinosaur discovered head first, for a change

A team of paleontologists has discovered a new dinosaur species they're calling Abydosaurus, which belongs to the group of gigantic, long-necked, long-tailed, four-legged, plant-eating dinosaurs such as Brachiosaurus.

In a rare twist, they recovered four heads – two still fully intact – from a quarry in Dinosaur National Monument in eastern Utah. Complete skulls have been recovered for only eight of more than 120 known varieties of sauropod"Their heads are built lighter than mammal skulls because they sit way out at the end of very long necks," said Brooks Britt, a paleontologist at Brigham Young University. "Instead of thick bones fused together, sauropod skulls are made of thin bones bound together by soft tissue. Usually it falls apart quickly after death and disintegrates."

Britt is a co-author on the discovery paper scheduled to appear in the journal Naturwissenshaften.

The lead author is Daniel Chure, a paleontologist at Dinosaur National Monument, who has no trouble boiling down the significance of the discovery.

"We've got skulls!" he shouted with sweeping hand gestures during a recent visit to the site.

BYU geology students and faculty resorted to jackhammers and concrete saws to cut through the hardened 105-million-year-old sandstone containing the bones. At one point the National Park Service called in a crew to blast away the overlying rock with explosives.

The skulls are temporarily on display at BYU's Museum of Paleontology, where visitors can also watch BYU students prepare other bones from Abydosaurus.

"The hardest bone I personally have worked on is a vertebra that was half-eroded before discovery and is so fragile that it crumbles if you look at it wrong," said Kimmy Hales, a geology major studying vertebrate paleontology at BYU. "The funnest project I have worked on was a set of five toe bones. Each toe bone was larger than my hand."

Analysis of the bones indicates that the closest relative of Abydosaurus is Brachiosaurus, which lived 45 million years earlier. The four Abydosaurus specimens were all juveniles.

Most of what scientists know about sauropods is from the neck down, but the skulls from Abydosaurus give a few clues about how the largest land animals to roam the earth ate their food.

"They didn't chew their food; they just grabbed it and swallowed it," Britt said. "The skulls are only one two-hundredth of total body volume and don't have an elaborate chewing system."

All sauropods ate plants and continually replaced their teeth throughout their lives. In the Jurassic Period, sauropods exhibited a wide range of tooth shapes. But by the end of the dinosaur age, all sauropods had narrow, pencil-like teeth.

Abydosaurus teeth are somewhere in between, reflecting a trend toward smaller teeth and more rapid tooth replacement.

The fossils were excavated from the Cedar Mountain Formation in Dinosaur National Monument near Vernal, Utah. The site is just a quarter of a mile away from the condemned visitor center that displays thousands of bones that remain in place on an uplifted slab of sandstone.

University of Michigan researchers John Whitlock and Jeffrey Wilson are also co-authors on the study.

What's in the name Abydosaurus mcintoshi?

The generic name refers to Abydos, the Greek name for the city along the Nile River (now El Araba el Madfuna) that was the burial place of the head and neck of Osiris, Egyptian god of life, death and fertility. Abydos alludes to the type specimen, which is a skull and neck found in a quarry overlooking the Green River. Sauros is the Greek word for lizard.

The specific name mcintoshi honors the American paleontologist Jack McIntosh for his contributions to the study of sauropod dinosaurs. In 1975 McIntosh debunked the myth of Brontosaurus, exposing it as a mixed-up skeleton with an Apatosaurus body and a Camarasaurus skull.

Source : Brigham Young University

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DNA sequencing unlocks relationships among flowering plants

The origins of flowering plants from peas to oak trees are now in clearer focus thanks to the efforts of University of Florida researchers.

A study appearing online this week in the Proceedings of the National Academy of Sciences unravels 100 million years of evolution through an extensive analysis of plant genomes. It targets one of the major moments in plant evolution, when the ancestors of most of the world's flowering plants split into two major groups. Together the two groups make up nearly 70 percent of all flowering plants and are part of a larger clade known as Pentapetalae, which means five petals. Understanding how these plants are related is a large undertaking that could help ecologists better understand which species are more vulnerable to environmental factors such as climate change.
Shortly after the two groups split apart, they simultaneously embarked upon a rapid burst of new species that lasted 5 million years. This study shows how those species are related and sheds further light on the emergence of flowering plants, an evolutionary phenomenon described by Charles Darwin as an abominable mystery.
"This paper and others show flowering plants as layer after layer of bursts of evolution," said Doug Soltis, study co-author and UF distinguished professor of biology. "Now it's falling together into two big groups."
Pentapetalae has enormous diversity and contains nearly all flowering plants. Its two major groups, superrosids and superasterids, split apart between 111 million and 98 million years ago and now account for more than 200,000 species. The superrosids include such familiar plants as hibiscus, oaks, cotton and roses. The superasterids include mint, azaleas, dogwoods and sunflowers.
Earlier studies were limited by technology and involved only four or five genes. Those studies hinted at the results found in the new study but lacked statistical support, said study co-author Pam Soltis, distinguished professor and Florida Museum of Natural History curator of molecular systematics and evolutionary genetics.
The new study at UF's Florida Museum of Natural History analyzed 86 complete plastid genome sequences from a wide range of plant species. Plastids are the plant cell component responsible for photosynthesis.
Previous genetic analyses of Pentapetalae failed to untangle the relationships among living species, suggesting that the plants diverged rapidly over 5 million years. Researchers selected genomes to sequence based on their best guess of genetic relationships from the previous sequencing work.
Genome sequencing is more time-consuming for plants than animals because plastid DNA is about 10 times larger than the mitochondrial DNA used in studying animal genomes. But continual improvements in DNA sequencing technology are now allowing researchers to analyze those larger amounts of data more quickly.
The study provides an important framework for further investigating evolutionary relationships by providing a much clearer picture of the deep divergence that led to the split within flowering plants, which then led to speciation in the two separate branches.
Eventually, researchers hope to match these evolutionary bursts with geological and climatic events in the earth's history. "I think we're starting to get to a point with a dated tree where we could start looking at what was happening at some of those time frames," Pam Soltis said.
Source : University of Florida

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An emotion detector for baby

Baby monitors of the future could translate infant cries, so that parents will know for certain whether their child is sleepy, hungry, needing a change, or in pain. Japanese scientists report details of a statistical computer program that can analyze a baby's crying in the International Journal of Biometrics.

As any new parent knows, babies have a very loud method of revealing their emotional state - crying. Unfortunately, the parenting handbook does not offer guidance on how to determine what the crying means. Parents sometimes learn with experience that their child's cries may be slightly different depending on their cause, whether hunger or discomfort. Now, engineers in Japan have turned to an approach to product design, known as kansei engineering, invented in the 1970s by Professor Mitsuo Nagamachi, Dean of Hiroshima International University, which aims to "measure" feelings and emotions.

Tomomasa Nagashima of the Department of Computer Science and Systems Engineering, at Muroran Institute of Technology, in Hokkaido and colleagues explain that the fundamental problem in building an emotion detector for baby's crying is that the baby cannot confirm verbally what its cries mean. Various researchers have tried to classify infant emotions based on an analysis of the crying pattern but with little success so far.

The team has employed sound pattern recognition approach that uses a statistical analysis of the frequency of cries and the power function of the audio spectrum to classify different types of crying. They were then able to correlate the different recorded audio spectra with a baby's emotional state as confirmed by the child's parents. In their tests recordings of crying babies with a painful genetic disorder, were used to make differentiating between the babies' pained cries and other types of crying more obvious. They achieved 100% success rate in a validation to classify pained cries and "normal" cries.

The research has developed a sound theoretical method for classification of infant emotions, although limited to a specific emotion, based on analysis of the audio spectra of the baby's cries. The technique might one day be incorporated into a portable electronic device, or app, to help parents or carers decide on a course of action when their child is crying.

Source : Inderscience Publishers

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Fish can recognize a face based on UV pattern alone

Two species of damselfish may look identical—not to mention drab—to the human eye. But that's because, in comparison to the fish, all of us are essentially colorblind. A new study published online on February 25th in Current Biology, a Cell Press publication, reveals that the fish can easily tell one species from another based entirely on the shape of the ultraviolet (UV) patterns on their faces.

Although scientists have long known that some animals have UV vision, the new findings suggest that this sense can be keener and perhaps more useful as a "communication channel" than had been anticipated, according to the researchers
"Researchers have been assuming for a long time that UV vision is not very good—and that it is only useful for detecting the presence and absence of UV light, or objects in front of UV bright backgrounds," said Ulrike Siebeck of the University of Queensland in Australia. "The exciting thing is that we can show that these fish can tell the difference between intricate UV patterns—something that was not expected based on previous assumptions."
In fact, researchers had some good reasons to doubt the precision of UV vision. The short wavelengths of light that characterize UV are prone to scattering in air and water. And even animals that can see in the UV range usually don't have all that many UV cones, or photoreceptors, in their eyes. But apparently nobody told that to the damselfish.
In the new experiments, Siebeck's team presented the very aggressive fish with two intruders, representing different species that vary in appearance only in their UV patterns. Those initial choice tests showed that the fish always attacked one species over the other. But, when the researchers took away the fishes' ability to see in UV, that preference between species disappeared.
The researchers next transferred the two species-specific UV patterns onto otherwise blank pieces of paper. They trained the fish to swim up to and nudge one of the patterns by offering food rewards. When the fish were later presented with both patterns, they still selected the pattern they had been trained on.
Put together, the two lines of evidence support the notion that the UV patterns are both necessary and sufficient for the fish to tell the two species apart.
The ability to see in this visual field is likely quite convenient for the fish, Siebeck said. "If you think about it in simple terms, fish have to be inconspicuous if they want to go undetected by their predators and prey, but at the same time, they have to be conspicuous if they want to attract the attention of potential mates, for example. Using UV patterns to do this is a clever way to maximize both at the same time—they are still inconspicuous to predators but very conspicuous to other fish with UV vision."
The researchers say the new findings now call for more detailed investigation of UV vision in damselfish and other UV-sighted animals, to find out just how well animals can see in this range, and over what distances. The researchers are also testing whether fish can tell different individuals—as opposed to whole species—apart based on fine-scale variation in their UV facial patterns.
Source : Cell Press

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Is an animal's agility affected by the position of its eyes?

New research from scientists in Liverpool has revealed the relationship between agility and vision in mammals. The study, published today in the Journal of Anatomy, sampled 51 species to compare the relationship between agility and vision between frontal eyed species, such as cats, to lateral-eyed mammals such as rabbits, to establish if the positioning of the eyes resulted in limitations to speed and agility.

"Footballers do it, cheetahs do it, and even sedentary academics can do it. We all have the ability to visually track an object whilst on the move and you don't give a second thought to the effort involved," explained co-author Dr Nathan Jeffery from the University of Liverpool. "As you walk or run your head swings up and down, tilts from side to side and rotates. Three semicircular canals of fluid found on each side of the skull sense these movements, one for each direction. These then send signals via the brain to three pairs of muscles that move the eyeball in the opposite direction and ensure that you can keep your eye on the ball, gazelle or the beer in your hand."
This process, known as the vestibulo-ocular reflex, is affected by the directions sensed by the canals and the pull directions of the eye muscles. In mammals, the eyes can be on the side of the head, as with rabbits, or at the front of the head like in cats, however the position of the canals is basically the same. In some mammals the brain must do extra calculations to adjust the signal from the canals to match the different pull directions of the eye muscles.
"In our study we wanted to find out if these extra calculations placed any limitations on how fast an animal could move," said co-author Phillip Cox. "We asked if there could be a point whereby, if an animal moves too quickly it could result in the brain being unable to adjust the signals from canal to muscle planes, which in turn would result in blurred vision." The work was funded by the Biotechnology and Biological Sciences Research Council.
The team used MRI scanners to analyse the arrangement of canals and eye muscles in 51 species of mammal including giraffes, camels and zebra, tree shrews, bats and sloths. Astonishingly, the team found that the position of canals and eye muscles had no effect on the ability to see clearly at speed. In theory, a Sloth could travel as fast as a Cheetah without blurring its vision.
The team also found evidence suggesting that the role of the extraocular muscles switches with changes of eye position. For instance, muscles that make up-down compensatory movements in frontal-eyed species appear aligned for torsional movements in lateral-eyed species. Before this, scientists had assumed that major rewiring of the connections was essential to adapt the reflex to changes of eye position.
"Switching between muscles offers an economical way of adapting the vestibulo-ocular reflex to changes of eye position without major rewiring of the connections or changes of canal orientations," concluded Dr Jeffery. "The mammalian brain can apparently cope with the extra demands placed on it whether the eyes are at the front, side or almost at the back of the head."
Source : Wiley-Blackwell

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Virus hybridization could create pandemic bird flu

MADISON — Genetic interactions between avian H5N1 influenza and human seasonal influenza viruses have the potential to create hybrid strains combining the virulence of bird flu with the pandemic ability of H1N1, according to a new study.

In laboratory experiments in mice, a single gene segment from a human seasonal flu virus, H3N2, was able to convert the avian H5N1 virus into a highly pathogenic form. The findings are reported the week of Feb. 22 in the online early edition of the Proceedings of the National Academy of Sciences.

"Some hybrids between H5N1 virus and seasonal influenza viruses were more pathogenic than the original H5N1 viruses. That is worrisome," says Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison and senior author of the new study.
The H5N1 bird flu virus has spread worldwide through bird populations and has caused 442 confirmed human cases and 262 deaths, according to the World Health Organization. To date, however, bird flu has not been able to spread effectively between people.
"H5N1 virus has never acquired the ability to transmit among humans, which is why we haven't had a pandemic. The worry is that the pandemic H1N1 virus may provide that nature in the background of this highly pathogenic H5N1 virus," says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine.
Two viruses infecting a single host cell can swap genetic material, or reassort, creating hybrid strains with characteristics of each parent virus.
Before the current study, hybrid viruses generated in lab studies had always been less virulent than parent strains. However, the new findings raise concerns that H5N1 and pandemic H1N1 viruses could reassort in individuals exposed to both viruses and generate an influenza strain that is both highly virulent and contagious.
The increased virulence seen in the new study seems to arise from one of the eight genes in the viral genome, called PB2, which is known to affect how well the bird flu virus grows in mammalian hosts, including humans. When tested in mice, the human virus version of PB2 swapped into H5N1 converted the avian virus to a highly pathogenic form.
The researchers say surveillance of viral populations is critical to monitor the potential emergence of highly pathogenic viral variants due to reassortment of avian and human influenza viruses. Their results, including identification of the PB2 segment as a key to enhanced virulence, offer information likely to be useful in the event of a pandemic caused by a hybrid avian-human influenza strain.
"With the new pandemic H1N1 virus, people sort of forgot about H5N1 avian influenza. But the reality is that H5N1 avian virus is still out there," Kawaoka says. "Our data suggests that it is possible there may be reassortment between H5 and pandemic H1N1 that can create a more pathogenic H5N1 virus."
Source : University of Wisconsin-Madison

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Left over cancer cell encourage cancer spread

Researchers with the University of Alabama at Birmingham (UAB) Comprehensive Cancer Center and UAB Department of Chemistry have won an $805,000 grant from the U.S. Department of Defense Breast Cancer Research Program to study whether dead cancer cells left over after treatment encourage cancer's spread to other parts of the body.The research centers on examining inactivated or altered genetic material (DNA) left in the body after breast-cancer cells are exposed to chemotherapy. UAB researchers say the resulting altered DNA may be the factor that activates the spread of living cancer cells to distant locations in the body – a deadly process called metastasis – through a specific molecular pathway.



Learning more about this metastasis pathway could lead to major improvements in prevention, treatment and follow-up care for millions of cancer patients, says Katri Selander, M.D., Ph.D., an assistant professor in the UAB Division of Hematology and Oncology and co-principal researcher on the grant.

"What if by killing cancer cells with chemotherapy we inadvertently induce DNA structures that make surviving cancers cells more invasive? The idea is tough to stomach," Selander says. "Fundamentally this question must be answered to advance the knowledge base and to know all the risks and benefits of cancer treatment.

"This research has the potential to reach across numerous scientific disciplines, and may one day improve the lives of patients worldwide."

Metastasis is the No. 1 cause of cancer recurrence and treatment failure.

The new grant expands on a research partnership between Selander and her team of researchers and those working in the laboratory of David Graves, Ph.D., chair of the UAB Department of Chemistry. Graves and his team are characterizing the DNA structures and other factors that induce metastasis in surviving cancer cells.

The pathway activated by the dead cancer cells is mediated in the body as a protein called toll-like receptor 9, or TLR9. This protein is present in the immune system and in many types of cancer. If TLR9 boosts metastasis, then researchers will work on finding targeted therapies that block or regulate this molecular pathway, Selander says.

UAB's grant from the Department of Defense Breast Cancer Research Program is designed to reward innovative research projects that could lead to major scientific and health advances.

Source : University of Alabama at Birmingham

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Insight into human decision making - Crayfish Model

Crayfish make surprisingly complex, cost-benefit calculations, finds a University of Maryland study, opening the door to a new line of research that may help unravel the cellular brain activity involved in human decisions.

The Maryland researchers conclude that crayfish make an excellent, practical model for identifying the specific neural circuitry and neurochemistry of decision making. They believe their study is the first to isolate individual crayfish neurons involved in value-based decisions. Currently, there's no direct way to do this with a human brain. The study will be published in the Proceedings of the Royal Society B, and is being released online today.

"Matching individual neurons to the decision making processes in the human brain is simply impractical for now," explains University of Maryland psychologist Jens Herberholz, the study's senior author. "History has shown that findings made in the invertebrate nervous systems often translate to more complex organisms. It's unlikely to be exactly the same, but it can inform our understanding of the human brain, nonetheless. The basic organization of neurons and the underlying neurochemistry are similar, involving serotonin and dopamine, for example."

Herberholz adds that his lab's work may inform ongoing studies in rodents and primates. "Combining the findings from different animal models is the only practical approach to work out the complexities of human decision making at the cellular level."

Specific findings and conclusions

The experiments offered the crayfish stark decisions – a choice between finding their next meal and becoming a meal for an apparent predator. In deciding on a course of action, they carefully weighed the risk of attack against the expected reward, Herberholz says.

Using a non-invasive method that allowed the crustaceans to freely move, the researchers offered juvenile Louisiana Red Swamp crayfish a simultaneous threat and reward: ahead lay the scent of food, but also the apparent approach of a predator. In some cases, the "predator" (actually a shadow) appeared to be moving swiftly, in others slowly. To up the ante, the researchers also varied the intensity of the odor of food.

How would the animals react? Did the risk of being eaten outweigh their desire to feed? Should they "freeze" – in effect, play dead, hoping the predator would pass by, while the crayfish remained close to its meal – or move away from both the predator and food?

To make a quick escape, the crayfish would flip their tails and swim backwards – an action preceded by a strong, measurable electric neural impulse. The specially designed tanks could non-invasively pick up and record these electrical signals. This allowed the researchers to identify the activation patterns of specific neurons during the decision-making process.

Although tail-flipping is a very effective escape strategy against natural predators, it adds critical distance between a foraging animal and its next meal.

The crayfish took decisive action in a matter of milliseconds. When faced with very fast shadows, they were significantly more likely to freeze than tail-flip away. The researchers conclude that there's little incentive for retreat when the predator appears to be moving too rapidly for escape, and the crayfish would lose its own opportunity to eat. This was also true when the food odor was the strongest, raising the benefit of staying close to the expected reward. A strong predator stimulus, however, was able to override an attractive food signal, and crayfish decided to flip away under these conditions.

"Our results indicate that when the respective values of tail-flipping and freezing change, the crayfish adjust their choices accordingly, thus preserving adaptive action selection," the study concludes. "We have now shown that crayfish, similar to organisms of higher complexity, integrate different sensory stimuli that are present in their environment, and they select a behavioural output according to the current values for each choice."

The next step is to identify the specific cellular and neurochemical mechanisms involved in crayfish decisions, which is more feasible in an animal with fewer and accessible neurons, Herberholz says. That research is now underway.

Source : University of Maryland

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Chimpanzees kill individuals to expand territory

Bands of chimpanzees violently kill individuals from neighboring groups in order to expand their own territory, according to a 10-year study of a chimp community in Uganda that provides the first definitive evidence for this long-suspected function of this behavior.

University of Michigan primate behavioral ecologist John Mitani's findings are published in the June 22 issue of Current Biology.

During a decade of study, the researchers witnessed 18 fatal attacks and found signs of three others perpetrated by members of a large community of about 150 chimps at Ngogo, Kibale National Park.

Then in the summer of 2009, the Ngogo chimpanzees began to use the area where two-thirds of these events occurred, expanding their territory by 22 percent. They traveled, socialized and fed on their favorite fruits in the new region.

"When they started to move into this area, it didn't take much time to realize that they had killed a lot of other chimpanzees there," Mitani said. "Our observations help to resolve long-standing questions about the function of lethal intergroup aggression in chimpanzees."

Mitani is the James N. Spuhler Collegiate Professor in the Department of Anthropology. His co-authors are David Watts, an anthropology professor at Yale University, and Sylvia Amsler, a lecturer in anthropology at the University of Arkansas at Little Rock. Amsler worked on this project as a graduate student at U-M.

Chimpanzees (along with bonobos) are humans' closest living relatives. Anthropologists have long known that they kill their neighbors, and they suspected that they did so to seize their land.

"Although some previous observations appear to support that hypothesis, until now, we have lacked clear-cut evidence," Mitani said.

The bouts occurred when the primates were on routine, stealth "boundary patrols" into neighboring territory. Amsler, who conducted field work on this project described one of the attacks she witnessed far to the northwest of the Ngogo territory. She and a colleague were following 27 adult and adolescent males and one adult female.

"They had been on patrol outside of their territory for more than two hours when they surprised a small group of females from the community to the northwest," Amsler said. "Almost immediately upon making contact, the adult males in the patrol party began attacking the unknown females, two of whom were carrying dependent infants."

The Ngogo patrollers seized and killed one of the infants fairly quickly. They fought for 30 minutes to wrestle the other from its mother, but unsuccessfully. The Ngogo chimpanzees then rested for an hour, holding the female and her infant captive. Then they resumed their attack.

"Though they were never successful in grabbing the infant from its mother, the infant was obviously very badly injured, and we don't believe it could have survived," Amsler said.

In most of the attacks in this study, chimpanzee infants were killed. Mitani believes this might be because infants are easier targets than adult chimpanzees.

Scientists are still not sure if the chimpanzees' ultimate motive is resources or mates. They haven't ruled out the possibility that the attacks could attract new females to the Ngogo community.

Mitani says these findings disprove suggestions that the aggression is due to human intervention. Lethal attacks were first described by renowned primatologist Jane Goodall who, along with other human observers, used food to gain the chimps' trust. Some researchers posited that feeding the animals might have affected their behavior. The Michigan researchers didn't use food.

He cautions against drawing any connections to human warfare and suggests instead that the findings could speak to the origins of teamwork.

"Warfare in the human sense occurs for lots of different reasons," Mitani said. "I'm just not convinced we're talking about the same thing.

"What we've done at the end of our paper is to turn the issue on its head by suggesting our results might provide some insight into why we as a species are so unusually cooperative. The lethal intergroup aggression that we have witnessed is cooperative in nature, insofar as it involves coalitions of males attacking others. In the process, our chimpanzees have acquired more land and resources that are then redistributed to others in the group."

The paper is titled "Lethal intergroup aggression leads to territorial expansion in wild chimpanzees." The research is funded by the Detroit Zoological Institute, the Little Rock Zoo, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation, the University of Michigan, the Wenner-Gren Foundation for Anthropological Research, and Yale University.

Source : University of Michigan

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Gene therapy reverses type 1 diabetes in mice

Researchers have developed an experimental cure for Type 1 diabetes, a disease that affects about one in every 400 to 600 children and adolescents. They will present their results in a mouse model of Type 1 diabetes on Sunday at The Endocrine Society's 92nd Annual Meeting in San Diego.

Using gene therapy, the team from Baylor College of Medicine in Houston tried to counter the two defects that cause Type 1 diabetes: autoimmune attack and destruction of the insulin-producing beta cells. They used nonobese diabetic mice, which spontaneously develop diabetes due to autoimmunity, just as humans do with Type 1 diabetes.

"A single treatment cured about 50 percent of the diabetic mice, restoring their blood sugar to normal so that they no longer need insulin injections," said study co-author Lawrence Chan, MD, DSc, chief of Baylor's diabetes, endocrinology and metabolism division.

Type 1 diabetes occurs when the body's immune system attacks and destroys the beta cells in the pancreas, the insulin "factory" of the body. The resulting near-complete deficiency of insulin—the hormone that controls blood sugar—leads to a buildup of high blood sugar and thus diabetes.

In past studies of their original gene therapy, Chan's group was able to stimulate new formation of beta cells in the liver and restore insulin production and normal blood sugar levels in more than 100 mice with chemically induced diabetes. However, in nonobese diabetic mice the treatment failed to reverse Type 1 diabetes because the mouse's immune system killed the newly formed beta cells, he said.

In this research, which was funded by the National Institute of Diabetes, Kidney and Digestive Diseases, Chan said they "added to the original gene therapy approach a protective gene that shields the newly formed beta cells from autoimmune attack." The added gene was for interleukin-10, an important regulator of the immune system. Past studies showed that interleukin-10 can prevent diabetes development in mice but cannot reverse the disease once it has developed because of the lack of beta cells.

However, when the researchers combined the gene therapy with interleukin-10 into a single intravenous injection, the treatment showed a complete reversal of diabetes in half of the mice during more than 20 months' follow-up. Although the therapy did not reverse autoimmunity throughout the body, it protected the new beta cells from the local destructive effect of autoimmunity, Chan explained.

"We developed a protective 'moat' around the new beta cells," he said. "We are now developing other strategies to try to fortify the newly formed beta cells and give them better weapons in addition to the moat, in order to increase the treatment's cure rate."

Why the gene therapy did not work in all the mice is unclear. However, Chan said the treated mice that did not have improvements in their blood sugar did gain weight and lived a little longer than untreated mice.

Source : The Endocrine Society

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The genetic secret of longevity.

Scientists have developed way of predicting how likely a person is to live beyond the age of 100.

The breakthrough, described in the journal Science, is based on 150 genetic "signposts" found in exceptionally long-lived people.

The researchers created a mathematical model, which takes information from these signposts to work out a person's chance of reaching 100.It is based on the largest study of centenarians in the world.This is a rare trait - only one in 6,000 people in industrialised countries reaches such a ripe old age. And 90% them are still disability free by the age of 93.

The researchers now think they have cracked the genetic secret of this longevity.The team originally embarked on their study in 1995. Since then, they have scanned the genomes of 1,000 centenarians.They identified genetic markers that are "most different" between centenarians and randomly selected individuals.

The research was led by Paola Sebastiani, a professor of biostatistics at Boston University, and Thomas Perls, associate professor of medicine, also at Boston University.

"We tested our model in an independent set of centenarians and achieved an accuracy of 77%," explained Professor Sebastiani.

"So out of 100 centenarians we could correctly predict the outcome of 77."

She said that the "23% error rate" indicated that, although "genetics is fundamental in exceptional longevity it's not the only thing"."So there may be other factors like environment or other lifestyles that may help people live longer and healthier lives."

Enriched lives

Professor Perls explained that a previous study had looked at longevity in a group of people belonging to the Seventh-day Adventist Church.

"Those individuals have probably among the highest average life expectancy that we know of in the US of 88 years," he said.

"They get there by virtue of the fact that they have a religion that asks them to be vegetarian, they regularly exercise, they don't drink alcohol, they tend to manage their stress well through religion and time with family and they don't smoke.

"To live the additional 10-15 years beyond the age of 88, our paper is indicating that genetics are playing an increasingly important role."

The scientists said that, when it came to genes associated with a predisposition to age-related diseases, centenarians and non-centenarians did not really differ.

"This is very surprising," said Professor Sebastiani. "It suggests that what makes these people live a very long life is not a lack of genetic predisposition to diseases, but rather an enrichment of longevity."
Lifespan website

Professor Perls said it was feasible that a simple test could be developed to screen people's chances of being so long-lived.

"I think that that's a possibility down the road," he said. "It brings up this whole field of personal medicine and being able to use genetic information in the future to help guide therapy."

But he added that there should be "a great deal of caution in thinking about what people might actually do with the information".

"Will that stop companies from going ahead and [developing some kind of chip-based test]? Probably not," he said,

"But we think it's really important to understand what people end up doing with this information, including thinking about social entitlements - that merits a lot more discussion."

Professor Sebastiani added: "We have a long list of things to do here.... to understand the real biology behind what we have found."
Continue reading the main story Elderly woman (SPL)

One of the co-authors of the Science paper is already building a free-to use website where people will be able to use the mathematical model.

On that site, which could be up and running within a week, people who know their genetic code could work out their predisposition to exceptional longevity.

"The site would provide some description of how to interpret the results in the right context," Professor Sebastiani explained.

Dr Jeffrey Barrett, a geneticist from the Wellcome Trust Sanger Institute in Cambridge, UK, cautioned that "subtle biases could make the test seem more accurate than it really is".

"Some of the genetic variants in this study are claimed to have much, much stronger effects on longevity than we've seen in similar studies of diabetes, heart disease and cancer," he told BBC News.

"Evaluation of the test by an independent laboratory will be the ultimate test of its accuracy."

Professor Perls summed up the findings as "a very optimistic message".

"Exceptional longevity is not this vacuous entity that no one can figure out," he said.

"I think we've made quite some inroads here in terms of demonstrating a pretty important genetic component to this wonderful trait, and this really opens the door to future research."

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Mile stone in memory study

New research led by the University of Leicester and published in a prestigious international scientific journal has revealed for the first time the mechanism by which memories are formed.

The study in the Department of Cell Physiology and Pharmacology found one of the key proteins involved in the process of memory and learning. The breakthrough study has potential to impact drug design to treat Alzheimer's disease.

The discovery was made in the University of Leicester laboratory of Professor Andrew Tobin, Professor of Cell Biology, who is a Wellcome Trust Senior Research Fellow.

The work was done in collaboration with other scientists and published online ahead of print in PNAS- the Proceedings of the National Academy of Sciences. The paper was authored by:

Benoit Poulin, Adrian Butcher, Phillip McWilliams, Julie-Myrtille Bourgognon, Robert Pawlak, Kok Choi Kong, Andrew Bottrill, Sharad Mistry and Andrew B. Tobin at the University of Leicester; Jürgen Wess at the National Institutes of Health and Elizabeth M. Rosethorne, Steven J. Charlton at Novartis Institutes for Biomedical Research.

Professor Tobin said: "The work, which was done wholly at the University of Leicester, is focused on the mechanisms by which we form memories. We found one of the key proteins involved in the process of memory and learning.

"This protein is present in the part of the brain in which memories are stored. We have found that in order for any memory to be laid down this protein, called the M3-muscarinic receptor, has to be activated.

"We have also determined that this protein undergoes a very specific change during the formation of a memory - and that this change is an essential part of memory formation. In this regard our study reveals at least one of the molecular mechanisms that are operating in the brain when we form a memory and as such this represents a major break through in our understanding of how we lay down memories.

"This finding is not only interesting in its own right but has important clinical implications. One of the major symptoms of Alzheimer's disease is memory loss. Our study identifies one of the key processes involved in memory and learning and we state in the paper that drugs designed to target the protein identified in our study would be of benefit in treating Alzheimer's disease."

Professor Tobin said there was tremendous excitement about the breakthrough the team has made and its potential application: "It has been fascinating to look at the molecular processes involved in memory formation. We were delighted not only with the scientific importance of our finding but also by the prospect that our work could have an impact on the design of drugs for the treatment of Alzheimer's disease."

Source : University of Leicester

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Watch it grow: Digital embryo gains wings

The scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, who 'fathered' the Digital Embryo have now given it wings, creating the Fly Digital Embryo. In work published today in Nature Methods, they were able to capture fruit fly development on film, and were the first to clearly record how a zebrafish's eyes and midbrain are formed. The improved technique will also help to shed light on processes and organisms, which have so far been under-studied because they could not be followed under a microscope.

"Non-transparent samples like the fruit fly embryo scatter light, so the microscope picks up a mixture of in-focus and out-of-focus signal– good and bad information, if you like," says Ernst Stelzer, whose group carried out the project at EMBL. "Our new technique enables us to discriminate between that good and bad information, so it allows us to record organisms which have so far been poorly studied, because of their unfortunate optical properties."

Philipp Keller, who co-led and conducted the work, and Ernst Stelzer overcame the difficulties caused by thick, opaque samples, by shining patterns of light on them, instead of the usual continuous light sheet. This generates an image with alternating light and dark stripes, unless the light bounces off the sample and changes direction, in which case this stripy pattern will be blurred. By taking multiple images of different phases of the light pattern, and combining them, a computer can filter out the effects of scattered light and generate an accurate image of the sample, thus enabling scientists to record images that were previously unobtainable.

By combining this approach with imaging along different angles, the scientists were able to obtain three-dimensional movies of the developing fruit fly embryo in spite of the fact that it is almost opaque.

The EMBL scientists were also able to extend their recordings of zebrafish development to an unprecedented level. They took around one million images to capture the first three days of zebrafish development from three different angles, generating films in which the formation of the animal's eyes and midbrain are clearly visible.

"Of course, getting such good images is nice for the human observer, but it's particularly crucial for computational analyses, like tracking cell movements and divisions as we do in the Digital Embryo," says Philipp Keller, now at the Janelia Farm Research Campus of the Howard Hughes Medical Institute in Ashburn, VA, USA.

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Lower tumor risk in stem cell therapies -eureka

One of the characteristics of embryonic stem cells is their ability to form unusual tumors called teratomas. These tumors, which contain a mixture of cells from a variety of tissues and organs of the body, are typically benign. But they present a major obstacle to the development of human embryonic stem cell therapies that seek to treat a variety of human ailments such as Parkinson's, diabetes, genetic blood disorders and spinal cord injuries.

Now a team of biologists at UC San Diego funded by a grant from the California Institute for Regenerative Medicine, the state's stem-cell funding agency, has discovered a way to limit the formation of teratomas.

In this week's issue of the Proceedings of the National Academy of Sciences, the researchers report that they have identified a new signaling pathway critical for unlimited self propagation of embryonic stem cells. Using small molecule compounds that inhibit this pathway, the scientists were able to dramatically reduce the potential of embryonic stem cells to form teratomas.

"Human stem cell therapy involves differentiating human embryonic stem cells into the kinds of cells needed for the treatment," said Yang Xu, a professor of biology who headed the team that published the report. "But this differentiation is never complete, meaning that the final product is a mixture of cells inevitably containing undifferentiated embryonic stem cells. So by transplanting these cells into a patient, there's clearly a risk of producing teratomas."

If researchers could halt the propagation of human embryonic stem cells during lineage-specific differentiation before they are transplanted, they could avoid the risk of producing teratomas.

"This is a proof of concept to show how we can avoid teratomas in human embryonic stem cell therapies by studying the basic biology of these cells," said Xu. "At this point, we only see a significant but partial effect because we are targeting only one pathway. Once we identify more pathways required for teratoma formation by embryonic stem cells, we might be able to completely suppress the formation of teratomas by targeting multiple pathways simultaneously."

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Clue in Cell aging Process - Eureka

The ability to combat some age-related diseases, such as cancer and diabetes, may rest with scientists unlocking clues about the molecular and cellular processes governing aging. The underlying theory is that if the healthy portion of an individual's life span can be extended, it may delay the onset of certain age-related diseases. In the search to understand these molecular processes, researchers at the University of Massachusetts Medical School have uncovered an important new DAF-16 isoform – DAF-16d/f – that collaborates with other DAF-16 protein isoforms to regulate longevity.

Part of the insulin signaling pathway, DAF-16 plays a critical role in a number of biological processes in C. elegans, including longevity, lipid metabolism, stress response and development, and is the center of a complex network of genes and proteins. Previous studies have identified the isoform – a different form of the same protein – DAF-16a as a regulator of longevity; genetically knocking down the DAF-16a isoform shortens C. elegans' life span. In a new study appearing in the July 7, advanced online edition of Nature, Heidi A. Tissenbaum, PhD, associate professor of molecular medicine, and colleagues in the Program in Gene Function and Expression at UMass Medical School, show that the newly discovered isoform DAF-16d/f works in concert with DAF-16a to promote organismal life span.

"Up until now, research has focused on the DAF-16a and DAF-16b isoforms," said Dr. Tissenbaum. "What we're able to show is that DAF-16a alone is insufficient for lifespan regulation. Moving forward, any discussion about the process of aging will have to include this new protein isoform."

To see the effect of DAF-16d/f on life span, lead author Dr. Eun-soo Kwon, a post-doctoral fellow in the Tissenbaum laboratory, increased expression of the DAF-16d/f and DAF-16a in C. elegans. These studies showed that worms with the overexpressed DAF-16d/f lived longest. Additional experiments reveal that worms expressing DAF-16d/f were also more tolerant to heat stress during development and store more fat.

Because the DAF-16 gene in C. elegans is homologous to the FOXO gene in mammals, it may provide clues to longevity in humans. "Understanding the molecular pathways of DAF-16 and other genes will give us insight into aging at both the cellular and organism levels," said Tissenbuam. "As we age, at a certain point, something happens that triggers age-related disease. If we can learn what these signals are, it's possible we can find a way to extend the healthy portion of a person's life span and potentially delay the onset of age-related diseases such as cancer, diabetes and Alzheimer's."

The next line of inquiry will explore whether an increase in life span correlates to the health of the worm. "It's possible that we're restoring life span, but we don't know the effect of doing so," said Tissenbaum. "We have to explore whether this increased lifespan is of the healthy portion of the lifespan."

Graduate student Sri Devi Narasimhan and post-doctoral fellow Dr. Kelvin Yen also contributed to this study.

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Biosynthesis of Mysterious 21st Amino Acid

Researchers at the RIKEN Systems and Structural Biology Center and the University of Tokyo have clarified the structural basis for the biosynthesis of selenocysteine (Sec), an amino acid whose encoding mechanism offers clues about the origins of the genetic alphabet. The findings deepen our understanding of protein synthesis and lay the groundwork for advances in protein design.

Oneof the most remarkable aspects of translation, the process whereby genetic information is converted into proteins in cells, is its universality: nucleotide triplets ("codons") encode a set of twenty amino acids that form the building blocks for all living organisms. Selenocysteine, the "21^st amino acid" whose antioxidant properties help prevent cellular damage, is a rare exception to this rule. Structurally similar to the amino acid serine (Ser) but with an oxygen atom replaced by the micronutrient selenium (Se), selenocysteine is synthesized through a complex juggling of the cell's translational machinery whose mechanisms remain poorly understood. Central to this multi-step process is a Sec-specific transfer RNA (tRNA^Sec) with an unusual structure that enables it to hijack the "stop codon" UGA to allow incorporation of selenocysteine during protein synthesis. In earlier work, the researchers identified features of tRNA^Sec that differentiate it from other tRNA, notably the peculiar structure of a domain called the D-arm, which appeared to act as an identification marker for recognition by the selenocysteine synthesis machinery. This time, the team analyzed the D-arm's role in the interaction of tRNA^Sec with O-phosphoseryl-tRNA kinase (PSTK), a protein whose selective phosphorylation is essential for selenocysteine encoding.
Using X-ray crystallography, the team showed for the first time that it is the unique structure of the tRNA^Sec D-arm which enables PSTK to distinguish tRNA^Sec from other tRNA. Reported in the August 13 issue of Molecular Cell (online August 12), the discovery clarifies a pivotal step in selenocysteine biosynthesis, shedding new light on the mysterious 21^st amino acid and the elaborate process by which it is created.

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Why Some Plants Flower in Spring, Autumn and Some in Summer

Scientists have uncovered a new piece in the puzzle about why some plants flower in spring/autumn and some in summer.A team of researchers from Warwick have isolated a gene responsible for regulating the expression of CONSTANS, an important inducer of flowering, in Arabidopsis.
'Being able to understand and ultimately control seasonal flowering will enable more predictable flowering, better scheduling and reduced wastage of crops', explained Dr Jackson.
Whilst the relationship between CONSTANS and flowering time in response to day length is well established, the mechanism controlling the expression of CONSTANS is still not fully understood.
The scientists present their work at the Society for Experimental Biology Annual Meeting in Prague.
Many plants control when they flower to coincide with particular seasons by responding to the length of the day, a process known as photoperiodism. A flowering mutant of Arabidopsis, which had an altered response to photoperiod, was used in the study led by Dr Stephen Jackson.
In the study funded by the BBSRC, the team identified the defective gene in the mutant plant that caused its abnormal flowering time.
They then cloned a working version of the gene, known as DAY NEUTRAL FLOWERING (DNF), from a normal Arabidopsis plant and introduced it into the mutant plant to restore its normal flowering response to day length.
The role of DNF in normal plant flowering is to regulate the CONSTANS gene. CONSTANS is activated only in the light and the plant is triggered to flower when CONSTANS levels rise above a certain threshold level during the daytime.
In normal plants, DNF represses the levels of CONSTANS until the day length is long enough and conditions are favourable for the survival of their seedlings. In mutant plants without an active DNF gene, CONSTANS is not repressed and they are able to flower earlier in the year, when days are still short.
The presence of the DNF gene has not yet been identified in species other than Arabidopsis but the scientists believe their on-going work may prove to have a wider significance for other species.
Scientists can override complex pathways that control flowering by artificially inducing or inhibiting key flowering genes such as DNF and CONSTANS. This can already be done in the laboratory by spraying an 'inducing agent' onto plants, stimulating them to flower early.
This could be used to extend the length of the harvesting season or to co-ordinate flowering or fruit production to a specific time. Growers already regulate the flowering of a few plants such as Chrysanthemum and Poinsettia, the latter specifically for Christmas and Easter.
Unravelling the complex pathways that control plant flowering will help scientists to understand and influence flowering patterns more effectively and in many different species.

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Magnetic solution to kill tumors

Though a valuable weapon against cancerous tumors, radiation therapy often harms healthy tissue as it tries to kill malignant cells. Now, Prof. Israel Gannot of Tel Aviv University's Department of Biomedical Engineering is developing a new way to destroy tumors with fewer side effects and minimal damage to surrounding tissue.

His innovative method, soon to be published in the journal Nanomedicine, uses heat to kill the tumor cells but leaves surrounding healthy tissue intact. Using specific biomarkers attached to individual tumors, Prof. Gannot's special mixture of nano-particles and antibodies locates and binds to the tumor itself.

"Once the nano-particles bind to the tumor, we excite them with an external magnetic field, and they begin to heat very specifically and locally," says Prof. Gannot. The magnetic field is manipulated to create a targeted rise in temperature, and it is this directed heat elevation which kills the tumors, he says.

The treatment has been proven effective against epithelial cancers, which can develop in almost any area of the body, such as the breast or lung. By using a special feedback process, also developed in his laboratory, the process can be optimized for individual treatment.

A cure without casualty

The specialized cocktail of nano-particles and antibodies is administered safely and simply, through topical local injection or injection into the blood stream. As an added benefit, the mixture washes out of the body without leaving a trace, minimizing side effects.

If clinical trials are successful, the technique may become a mainstay of patient care. The nano-particles themselves are already FDA-approved, and according to Prof. Gannot, the method is effective almost any type of tumor, as long as its specific markers and its antibodies can be identified.

The countdown to demolition

In addition to being minimally invasive, this treatment boasts sheer speed. It can be applied during an out-patient procedure ― the entire technique lasts only six hours ― which allows patients to recuperate in the comfort of their own homes.

Prof. Gannot is currently applying his technique to cell lines and to ex vivo tissues and tissue-like substitutes in his lab, and plans to start in vivo experiments by next year.
Source : American Friends of Tel Aviv University

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Inject in to the Single cell

Duke University physicists have developed a way to produce sharp fluid jets with enough precision that they can inject material into a single, living cell. The technique promises a way to deliver drugs to cells one at a time, which is likely to be very valuable for research involving stem cells and other cellular-level studies. The research appears in the current issue of the APS journal Physical Review Letters.

The physicists produced the jets by focusing lasers into a fluid surrounding a target cell. The lasers heated molecules of a blue dye dissolved in the fluid, which in turn created tiny bubbles to rapidly grow and collapse. When these sorts of bubbles are produced individually, they create shock waves that spread throughout the liquid. But producing two adjacent bubbles in rapid succession results in small, powerful jets capable of poking tiny holes, measuring only 0.2 millionths of a meter across, in cell membranes.

The researchers confirmed that the jets allowed the introduction of fluids into the cell by checking for signs of the blue dye inside the pierced cells. The dye is toxic, and it killed the pierced cells, but the holes the jets produced were small enough that it's likely that the jets will offer a way to inject live cells with nontoxic substances without significantly damaging them.

Claus-Deiter Ohl of Nanyang Technological University in Singapore provides further information about the fluid jets and related research in a Viewpoint article in the current edition of APS Physics (physics.aps.org).

Source : American Physical Society

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