Tuesday, July 14, 2009

STANFORD DISCOVERY PINPOINTS NEW CONNECTION BETWEEN CANCER CELLS, STEM CELLS

0 comentarios
A molecule called telomerase, best known for enabling unlimited cell division of stem cells and cancer cells, has a surprising additional role in the expression of genes in an important stem cell regulatory pathway, say researchers at the Stanford University School of Medicine. The unexpected finding may lead to new anticancer therapies and a greater understanding of how adult and embryonic stem cells divide and specialize.

“Telomerase is the factor that accounts for the unlimited division of cancer cells,” said Steven Artandi, MD, PhD, associate professor of hematology, “and we’re very excited about what this connection might mean in human disease.” Artandi is the senior author of the research, published in the July 2 issue of the journal Nature. He is also a member of Stanford’s Cancer Center.

In many ways, telomerase is the quintessential molecule of mystery — hugely important and yet difficult to pin down. Telomerase was known to stabilize telomeres, special caps that protect the ends of chromosomes. It stitches short pieces of DNA on these chromosome ends in stem cells and some immune cells, conferring a capacity for unlimited cell division denied to most of the body’s other cells. Its importance is highlighted by the fact that it is inappropriately activated in more than 90 percent of cancer cells, suggesting that drugs or treatments that block telomerase activity may be effective anticancer therapies. However, its vast size, many components and relative rarity — it is not expressed in most of the body’s cells — hinder attempts to learn more about it.

Artandi and his lab have spent many years identifying and studying the components of the telomerase complex. In this most recent study, they were following up on a previous finding suggesting that one part, a protein called TERT, was involved in more than just maintaining telomeres. They had discovered that overexpressing TERT in the skin of mice stimulated formerly resting adult stem cells to divide — even in the absence of other telomerase components. “This was a pretty clear hint that TERT was involved in something more than just telomere maintenance,” he said.

Artandi and his colleagues recognized that the cells’ response to TERT mimicked that seen when another protein, beta-catenin, was overexpressed in mouse skin. Beta-catenin is a component of a vital signaling cascade known as the Wnt pathway, which is important in development, stem cell maintenance and stem cell activation. Stanford developmental biologist and professor Roeland Nusse, PhD, a collaborator on the current study, identified the first Wnt molecule in 1982.

In this study, Artandi and his colleagues purified the TERT protein from cultured human cells and found that it was associated with a chromatin-remodeling protein implicated in the Wnt pathway. They showed that overexpression of TERT in the presence of the remodeling protein enhanced the expression of Wnt-inducible genes. Finally, they found that TERT is required for mouse embryonic stem cells to respond appropriately to Wnt signals and that blocking TERT expression impairs the development of frog embryos.
“This is completely novel,” said Artandi, who went on to show that TERT physically occupies the upstream promoter regions of the genes. “No one had any idea that TERT was directly regulating the Wnt pathway.” He speculates that interfering with the protein’s Wnt-associated activity may be a faster way to inhibit cancer cells than blocking telomerase activity, which depends on the gradual shortening of telomeres with each cell division.

“The Wnt pathway and telomerase activity are two separate but coherent functions in stem cell self-renewal and cancer cell proliferation,” said Artandi. “Nature evolved a way to connect these two crucial functions by recruiting a component of telomerase directly into the Wnt pathway.” The researchers are now investigating what role TERT may play in normal and cancerous cells.

Stanford School of Medicine

NEW CLASS OF BLACK HOLES DISCOVERED

0 comentarios

A new class of black hole, more than 500 times the mass of the Sun, has been discovered in a distant galaxy approximately 290 million light years from Earth.

The international team, which includes STFC funded astronomers at the University of Leicester, reported their findings in the journal Nature.

Until now, identified black holes have been either super-massive (several million to several billion times the mass of the Sun) in the centre of galaxies, or about the size of a typical star (between three and 20 Solar masses).

The new discovery is the first solid evidence of a new class of medium-sized black holes. The team, led by astrophysicists at the Centre d'Etude Spatiale des Rayonnements in France, detected the new black hole with the European Space Agency's XMM-Newton X-ray space telescope.

"While it is widely accepted that stellar mass black holes are created during the death throes of massive stars, it is still unknown how super-massive black holes are formed," says the lead author of the paper, Dr Sean Farrell, now based at the Department of Physics and Astronomy at the University of Leicester.

He added: "One theory is that super-massive black holes may be formed by the merger of a number of intermediate mass black holes. To ratify such a theory, however, you must first prove the existence of intermediate black holes.

“This is the best detection to date of such long sought after intermediate mass black holes. Such a detection is essential. While it is already known that stellar mass black holes are the remnants of massive stars, the formation mechanisms of supermassive black holes are still unknown.”

"The identification of HLX-1 is therefore an important step towards a better understanding of the formation of the super-massive black holes that exist at the centre of the Milky Way and other galaxies."

A black hole is a remnant of a collapsed star with such a powerful gravitational field that it absorbs all the light that passes near it and reflects nothing.

It had been long believed by astrophysicists that there might be a third, intermediate class of black holes, with masses between a hundred and several hundred thousand times that of the Sun. However, such black holes had not been reliably detected until now.

This new source, dubbed HLX-1 (Hyper-Luminous X-ray source 1), lies towards the edge of the galaxy ESO 243-49. It is ultra-luminous in X-rays, with a maximum X-ray brightness of approximately 260 million times that of the Sun.

The X-ray signature of HLX-1 and the lack of a counterpart in optical images confirm that it is neither a foreground star nor a background galaxy, and its position indicates that it is not the central engine of the host galaxy.

Using XMM-Newton observations carried out on the 23rd November 2004 and the 28th November 2008, the team showed that HLX-1 displayed a variation in its X-ray signature. This indicated that it must be a single object and not a group of many fainter sources. The huge radiance observed can only be explained if HLX-1 contains a black hole more than 500 times the mass of the Sun. No other physical explanation can account for the data.

(Photo: Heidi Sagerud)

Science and Technology Facilities Council

INTENSE HEAT KILLED THE UNIVERSE'S WOULD-BE GALAXIES

0 comentarios

Millions of would-be galaxies failed to develop after being exposed to intense heat from the first stars and black holes formed in the early Universe, according to new research funded by Science and Technology Facilities Council (STFC) and the Japanese Society for the Promotion of Science.

Our Milky Way galaxy only survived because it was already immersed in a large clump of dark matter which trapped gases inside it, scientists led by Durham University’s Institute for Computational Cosmology (ICC) found.

The researchers said that the early Milky Way, which had begun forming stars, held on to the raw gaseous material from which further stars would be made. This material would otherwise have been evaporated by the high temperatures generated by the “ignition” of the Universe about half-a-billion years after the Big Bang.

Tiny galaxies, inside small clumps of dark matter, were blasted away by the heat which reached approximate temperatures of between 20,000 and 100,000 degrees centigrade, the scientists, including experts at Japan’s University of Tsukuba, said.

Dark matter is thought to make up 85 per cent of the Universe’s mass and is believed to be one of the building blocks of galaxy formation.

Using computer simulations carried out by the international Virgo Consortium (which is led by Durham) the scientists examined why galaxies like the Milky Way have so few companion galaxies or satellites.

Astronomers have found a few dozen small satellites around the Milky Way, but the simulations revealed that hundreds of thousands of small clumps of dark matter should be orbiting our galaxy.

The scientists said the heat from the early stars and black holes rendered this dark matter barren and unable to support the development of satellite star systems.

Joint lead investigator Professor Carlos Frenk, Director of the Institute for Computational Cosmology, at Durham University, said: “The validity of the standard model of our Universe hinges on finding a satisfactory explanation for why galaxies like the Milky Way have so few companions.

“The simulations show that hundreds of thousands of small dark matter clumps should be orbiting the Milky Way, but they didn’t form galaxies.

“We can demonstrate that it was almost impossible for these potential galaxies to survive the extreme heat generated by the first stars and black holes.

“The heat evaporated gas from the small dark matter clumps, rendering them barren. Only a few dozen front-runners which had a head start on making stars before the Universe ignited managed to survive.”

By providing a natural explanation for the origin of galaxies, the simulations support the view that cold dark matter is the best candidate for the mysterious material believed to make up the majority of our Universe, the scientists added.

It is now up to experimental physicists to either find this dark matter directly or to make it in a particle accelerator such as the Large Hadron Collider at CERN.

Professor Frenk, added: “Identifying the dark matter is not only one of the most pressing problems in science today, but also the key to understanding the formation of galaxies.”

Joint lead investigator Dr Takashi Okamoto from the University of Tsukuba said: “These are still early days in trying to make realistic galaxies in a computer, but our results are very encouraging.”

(Photo: Jim Geach (Durham University) and Rob Crain (CAS/Swinburne University of Technology))

Science and Technology Facilities Council

STUDY OF FLOWER COLOR SHOWS EVOLUTION IN ACTION

0 comentarios

Scientists at UC Santa Barbara have zeroed in on the genes responsible for changing flower color, an area of research that began with Gregor Mendel's studies of the garden pea in the 1850's.

In an article published recently in the Proceedings of the National Academies of Sciences, two researchers document their studies of the evolution of columbine flowers in North America. They studied red columbines pollinated by hummingbirds, and white or yellow columbines pollinated by hawkmoths. They believe that a color shift from red to white or yellow has happened five times in North America.

"What is important in this research is that hawkmoths mostly visit –– and pollinate –– white or pale flowers," said senior author Scott A. Hodges, professor of ecology, evolution and marine biology at UCSB. "We have shown experimentally that hawkmoths prefer these paler colors."

When a plant population shifts from being predominantly hummingbird-pollinated where flowers are red, to hawkmoth-pollinated, natural selection works to change the flower color to white or yellow, he explained.

"Ultimately we want to know if evolution can be predictable," said Hodges. "In other words, we want to know if each time there is an evolutionary change in flower color, does it happen in the same way? Having identified all the genes that are intimately involved with making red and blue columbines now allows us to determine how these evolutionary transitions have occurred."

In earlier research, Hodges showed that flowers evolve in a predictable fashion to match the mouthparts of pollinating birds and insects. Thus the pollinators of the yellow columbine flower, A. longissima, are predicted to have exceptionally long tongues to reach the nectar at the bottom.

(Photo: George Foulsham, Public Affairs, UCSB)

UC Santa Barbara

SCIENTISTS: SALAMANDERS, REGENERATIVE WONDERS, HEAL LIKE MAMMALS, PEOPLE

0 comentarios
The salamander is a superhero of regeneration, able to replace lost limbs, damaged lungs, sliced spinal cord — even bits of lopped-off brain.

But it turns out that remarkable ability isn’t so mysterious after all — suggesting that researchers could learn how to replicate it in people.

Scientists had long credited the diminutive amphibious creature’s outsized capabilities to “pluripotent” cells that, like human embryonic stem cells, have the uncanny ability to morph into whatever appendage, organ or tissue happens to be needed or due for a replacement.

But in a paper in the journal Nature, a team of seven researchers, including a University of Florida zoologist, debunks that notion. Based on experiments on genetically modified axolotl salamanders, the researchers show that cells from the salamander’s different tissues retain the “memory” of those tissues when they regenerate, contributing with few exceptions only to the same type of tissue from whence they came.

Standard mammal stem cells operate the same way, albeit with far less dramatic results — they can heal wounds or knit bone together, but not regenerate a limb or rebuild a spinal cord. What’s exciting about the new findings is they suggest that harnessing the salamander’s regenerative wonders is at least within the realm of possibility for human medical science.

“I think it’s more mammal-like than was ever expected,” said Malcolm Maden, a professor of biology, member of the UF Genetics Institute, and author of the paper. “It gives you more hope for being able to someday regenerate individual tissues in people.”

Also, the salamanders heal perfectly, without any scars whatsoever, another ability people would like to learn how to mimic, Maden said.

Axolotl salamanders, originally native to only one lake in central Mexico, are evolutionary oddities that become sexually reproducing adults while still in their larval stage. They are useful scientific models for studying regeneration because, unlike other salamanders, they can be bred in captivity and have large embryos that are easy to work on.

When an axolotl loses, for example, a leg, a small bump forms over the injury called a blastema. It takes only about three weeks for this blastema to transform into a new, fully functioning replacement leg — not long considering the animals can live 12 or more years.

The cells within the blastema appear embryonic-like and originate from all tissues around the injury, including the cartilage, skin and muscle. As a result, scientists had long believed these cells were pluripotential — meaning they came from a variety of sites and could make a variety of things once functioning in their regenerative mode.

Maden and his colleagues at two German institutions tested that assumption using a tool from the transgenic kit: the GFP protein. When produced by genetically modified cells, GFP proteins have the useful quality of glowing livid green under ultraviolet light. This allows researchers to follow the origin, movement and destination of the genetically modified cells.

The researchers experimented on both adult and embryonic salamanders.

With the embryos, the scientists grafted transgenic tissue onto sites already known to develop into certain body parts, then observed how and where the cells organized themselves as the embryo developed. This approach allowed them to see, literally, what tissues the transgenic tissue made. In perhaps the most vivid result, the researchers grafted GFP-modified nerve cells onto the part of the embryo known to develop into the nervous system. Once the creatures developed, ultraviolet light exams of the adults revealed the GFP cells stretched only along nerve pathways — like glowing green strings throughout the body

With the adults, they took tissue from specific parts or organs from transgenic GFP-producing axolotls, grafted it onto normal axolotls, then cut away a chunk of the grafted tissue to allow regeneration. They could then determine the fate of the grafted green cells in the emerging blastema and replacement tissue.

The researchers’ main conclusion: Only ‘old’ muscle cells make ‘new’ muscle cells, only old skin cells make new skin cells, only old nerve cells make new nerve cells, and so on. The only hint that the axolotl cells could revamp their function came with skin and cartilage cells, which in some circumstances seemed to swap roles, Maden said.

Maden said the findings will help researchers zero in on why salamander cells are capable of such remarkable regeneration. “If you can understand how they regenerate, then you ought to be able to understand why mammals don’t regenerate,” he said.

Maden said UF researchers will soon begin raising and experimenting on transgenic axolotls at UF as part of the The Regeneration Project, an effort to treat human brain and other diseases by examining regeneration in salamanders, newts, starfish and flatworms.

University of Florida

PLANTS PUT LIMIT ON ICE AGES

0 comentarios
When glaciers advanced over much of the Earth’s surface during the last ice age, what kept the planet from freezing over entirely? This has been a puzzle to climate scientists because leading models have indicated that over the past 24 million years geological conditions should have caused carbon dioxide levels in the atmosphere to plummet, possibly leading to runaway “icehouse” conditions. Now researchers writing in the July 2, 2009, Nature report on the missing piece of the puzzle – plants.

“Atmospheric CO2 concentrations have been remarkably stable over the last 20 or 25 million years despite other changes in the environment,” says co-author Ken Caldeira of the Carnegie Institution’s Department of Global Ecology. “We can look to land plants as the primary buffering agent that’s held CO2 in such a narrow range during this time.”

The research team, led by Mark Pagani of Yale University, found that the critical role of plants in the chemical breakdown and weathering of rocks and soil gave them a strong influence on carbon dioxide levels. It was a link that earlier studies had missed.

Over geologic time, large volumes of carbon dioxide have been released into the atmosphere by volcanoes. This would cause CO2 to build up in the atmosphere were it not for countervailing geologic processes of sedimentation, which bury carbon-containing minerals in the crust, sequestering it from the atmosphere. The overall rate of sedimentation is controlled by the upthrust of mountains and the erosion and chemical breakdown of their rocks. The rise of the Andes, Himalayas, Tibetan Plateau, and mountain ranges in western North America over the past 25 million years would have been expected to have cause faster weathering and erosion, and therefore a faster burial of carbon drawn from the atmosphere. But the stability of carbon dioxide levels indicates that this didn’t happen. Why not?

This is where the plants come in. “The rates of weathering reactions are largely controlled by plants. Their roots secrete acids that dissolve minerals, they hold soils, and they increase the amount of carbon dissolved in groundwater,” says Caldeira. “But when levels of carbon dioxide get too low, the plants basically suffocate and the weathering slows down. That means less sediment is eroded from the uplands and less carbon can be buried. It’s a negative feedback on the system that has kept carbon dioxide levels from dropping too low.”

Extremely low carbon dioxide levels would have reduced the atmosphere’s ability to retain heat, putting the planet into a deep freeze. “So you could say that by limiting the drawdown of CO2 by chemical weathering and sedimentation, plants saved the planet from freezing over,” says Caldeira.

Could plants save us from rising carbon dioxide from human emissions and harmful greenhouse warming? No, says Caldeira. “We are releasing CO2 to the atmosphere about 100 times faster than all the volcanoes in the world put together. While these weathering processes will eventually remove the CO2 we are adding to the atmosphere, they act too slowly to help us avoid dangerous climate change. It will take hundreds of thousands of years for these rock weathering processes to remove our fossil fuel emissions from the atmosphere.”

Carnegie Institute for Science

SCIENTISTS 'REBUILD' GIANT MOA USING ANCIENT DNA

0 comentarios
Researchers from the University of Adelaide and Landcare Research in New Zealand have identified four different moa species after retrieving ancient DNA from moa feathers believed to be at least 2500 years old.

The giant birds - measuring up to 2.5 metres and weighing 250 kilograms - were the dominant animals in New Zealand's pre-human environment but were quickly exterminated after the arrival of the Maori around 1280AD.

PhD student Nicolas Rawlence from the University's Australian Centre for Ancient DNA says until now, the scientific community has not known what the 10 different species of moa looked like. "By using ancient DNA we have been able to connect feathers to four different moa species," he says.

The researchers compared the feathers to others found in the sediments from red-crowned parakeets that are still living today, determining they had not faded or changed in colour. They then reconstructed the appearance of the stout-legged moa, heavy-footed moa, upland moa and the South Island giant moa.

Their findings were published in the Proceedings of the Royal Society of London Series B.

"The surprising thing is that while many of the species had a similar, relatively plain brown plumage for camouflage, some had white-tipped feathers to create a speckled appearance," Mr Rawlence says.

A co-author of the study, Dr Jamie Wood from Landcare Research, says it is likely that the drab colouring was driven by selection to avoid predation by the extinct Haast's eagle, the largest and most powerful eagle in the world.

The research team also demonstrated that it is possible to retrieve DNA from all parts of the ancient feathers, not just the tip of the quill, as previously thought.

"This important finding opens the way to study DNA from museum bird skins while causing almost no damage to these valuable specimens, just by clipping a small part of a single feather," says Dr Kyle Armstrong from the Australian Centre for Ancient DNA (ACAD).

ACAD Director Professor Alan Cooper says this finding suggests it may be possible to reconstruct the appearance of other extinct birds using feathers from fossil deposits.

"There are so many enigmatic extinct species that it would be great to see `clothed'," Professor Cooper says.

University of Adelaide

UCLA COLLABORATION IDENTIFIES IMMUNE SYSTEM LINK TO SCHIZOPHRENIA

0 comentarios
Now following on their earlier work that identified three gene locations that may be implicated in schizophrenia, researchers at UCLA and colleagues from around the world have, for the first time, identified additional genes that confirm what scientists have long suspected — that the immune system may play a role in the development of the disorder. Further, they have also identified genetic anomalies that disrupt the cellular pathways involved in brain development, memory and cognition, all markers of schizophrenia.

The research appeared in the July 1 online edition of the journal Nature.

Roel Ophoff, the co-lead author and an assistant professor at the Center for Neurobehavioral Genetics at the UCLA Semel Institute for Neuroscience and Human Behavior, and his collaborators from nearly 50 institutions worldwide, performed a genome-wide scan of 2,663 people diagnosed with schizophrenia and 13,498 controls from eight European locations. They were looking for single nucleotide polymorphisms (SNP), genetic variations that are commonly present in the general population but more often present in those suffering from the disorder. In total, nearly 314,000 SNPs were included in their analysis.

They found significant associations with genetic markers on the Major Histocompatibility Complex (MHC), a group of genes that controls several aspects of the immune response. Further, they discovered additional variations in two other genes, called NRGN and TCF4, which points to perturbation of pathways involved in brain development, memory and cognition.

"This is another step forward in understanding the biological basis of this disorder, one that robs people of their lives," said Ophoff, who holds a joint appointment at the University of Utrecht, The Netherlands. "It also shows the importance of worldwide collaborations for the study of schizophrenia genetics, because it allows us to do very large numbers of scans."

The findings are significant yet not without challenge, said Ophoff, since the study aimed at the "common variants" in the human genome. "In other words," he said, "these are not rare mutations present in only a few individuals, but these genetic variants are abundantly present in the population. Anybody could carry this variant, but that doesn't mean they will necessarily develop the disease. Yet, when you look at the population at large, these variants are more often present in patients than in healthy control subjects."

And that's important, he noted, in developing new techniques to thwart the disease. "Knowing these specific genes are involved in the pathway leading to schizophrenia provides unique clues as to which molecular mechanisms are involved," he said.

While the association between schizophrenia and the immune system has long been suspected, the evidence for it has, until now, been mostly circumstantial. And impaired cognitive and memory functions are increasingly being recognized as core features of schizophrenia, which are poorly addressed by current medications.

"The three common genetic variants we describe, then, which we feel predisposes certain individuals to schizophrenia, have the potential to be translated into targets for the development of new and novel medications," Ophoff said.

UCLA

THE LEAST SEA ICE IN 800 YEARS

0 comentarios

New research, which reconstructs the extent of ice in the sea between Greenland and Svalbard from the 13th century to the present indicates that there has never been so little sea ice as there is now. The research results from the Niels Bohr Institute, among others, are published in the scientific journal, Climate Dynamics.

There are of course neither satellite images nor instrumental records of the climate all the way back to the 13th century, but nature has its own 'archive' of the climate in both ice cores and the annual growth rings of trees and we humans have made records of a great many things over the years - such as observations in the log books of ships and in harbour records. Piece all of the information together and you get a picture of how much sea ice there has been throughout time.

"We have combined information about the climate found in ice cores from an ice cap on Svalbard and from the annual growth rings of trees in Finland and this gave us a curve of the past climate" explains Aslak Grinsted, geophysicist with the Centre for Ice and Climate at the Niels Bohr Institute at the University of Copenhagen.

In order to determine how much sea ice there has been, the researchers needed to turn to data from the logbooks of ships, which whalers and fisherman kept of their expeditions to the boundary of the sea ice. The ship logbooks are very precise and go all the way back to the 16th century. They relate at which geographical position the ice was found. Another source of information about the ice are records from harbours in Iceland, where the severity of the winters have been recorded since the end of the 18th century.

By combining the curve of the climate with the actual historical records of the distribution of the ice, researchers have been able to reconstruct the extent of the sea ice all the way back to the 13th century. Even though the 13th century was a warm period, the calculations show that there has never been so little sea ice as in the 20th century.

In the middle of the 17th century there was also a sharp decline in sea ice, but it lasted only a very brief period. The greatest cover of sea ice was in a period around 1700-1800, which is also called the 'Little Ice Age'.

"There was a sharp change in the ice cover at the start of the 20th century," explains Aslak Grinsted. He explains, that the ice shrank by 300.000 km2 in the space of ten years from 1910-1920. So you can see that there have been sudden changes throughout time, but here during the last few years we have had some record years with very little ice extent.

"We see that the sea ice is shrinking to a level which has not been seen in more than 800 years", concludes Aslak Grinsted.

(Photo: NASA/GSFC)

University of Copenhagen

Followers

Archive

 

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