Reversing skin aging by gene blockade

Researchers at the Stanford University School of Medicine have reversed the effects of aging on the skin of mice, at least for a short period, by blocking the action of a single critical protein.

The work could one day be useful in helping older people heal from an injury as quickly as they did when they were younger, said senior author Howard Chang, MD, PhD, assistant professor of dermatology. However, Chang and his colleagues warned their finding will likely be useful in short-term therapies in older people but not as a potential fountain of youth.
The work backs up the theory that aging is the result of specific genetic changes rather than accumulated wear and tear, Chang said. What's more, those genetic changes can be reversed even late in life.

"The implication is that the aging process is plastic and potentially amenable to intervention," Chang said. The results will be published in the Dec. 15 issue of the journal Genes and Development.

The work came about thanks to existing data from experiments using microarrays, which detect the activity of all genes in a cell. In past experiments, researchers have found a large number of diverse genes that become either more active or less active in older people.
Chang and graduate student Adam Adler, the study's first author, searched through this existing data to see if those age-related genes had anything in common. It turned out that their activity gets dialed up or down with the help of the protein called NF-kappa-B.

Chang said people had long known that NF-kappa-B winds its way into a cell's nucleus to control which genes were active. What they didn't know is that many of those genes regulated by the protein have a role in aging. Chang and Adler tested whether blocking the activity of NF-kappa-B in the skin of older mice for two weeks had a youthful effect. "We found a pretty striking reversal to that of the young skin," Chang said.

First they looked at the genetic changes resulting from blocking NF-kappa-B. After two weeks, the skin of 2-year-old mice had the same genes active as cells in the skin of newborn mice-a striking difference when compared with the skin of a normal 2-year-old mouse. The skin looked more youthful too. It was thicker and more cells appeared to be dividing, much like the skin of a younger mouse.

Chang and Adler caution that their findings aren't likely to be the source of the long-sought fountain of youth. That's because they don't know if the rejuvenating effects of NF-kappa-B are long-lasting. Also, the protein has roles in cancer, the immune system and a range of other functions throughout the body. Suppressing the protein on a long-term basis could very well result in cancers or other diseases that undermine its otherwise youthful effect.

"You might get a longer lifespan but at the expense of something else," Chang said.
Instead, the researchers believe their work could point to a way of helping older people heal more quickly after surgery or boost organ function during illness. These short-term applications aren't as likely to risk side effects that could accompany blocking such a critical protein.

Source: Stanford University School of Medicine

Dark energy -- 10 years on

Three quarters of our universe is made up of some weird, gravitationally repulsive substance that was only discovered ten years ago – dark energy. This month in Physics World, Eric Linder and Saul Perlmutter, both at the University of California at Berkeley, reveal how little we know about dark energy and describe what advances in our knowledge of dark energy we can expect in the coming decade from a series of planned space missions.

Perlmutter was the leader of one of the two separate teams of astrophysicists who concluded, from watching distant supernovae, that the cosmic expansion was accelerating and not slowing under the influence of gravity, as was previously thought. The two teams' finding confirmed just how little we know about our universe.

The two teams' discovery has led to the creation of the "concordance model" of the universe, which states that 75 per cent of our universe is made up of dark energy, 21 per cent of dark matter, another substance we know little about, with only a remaining four per cent being made up of matter that we do understand. The most conventional explanation is that dark energy is some kind of "cosmological constant" that arises from empty space not being empty, but having an energy as elementary particles pop in and out of existence.

Since the first evidence for the accelerating universe was made public in early 1998, astrophysicists have provided further evidence to shore up the findings and advances in the measurement methods bode well for increasing our understanding in the future.
Galaxies and the cosmic background hold some significant clues. Equipment that can make a more robust comparison between galaxy patterns across the sky and investigate temperature fluctuations in the cosmic microwave background, helping trace the pattern of galaxy formation, is being made available. Methods for further observation of supernovae are expanding and improving too.

Eric Linder and Saul Perlmutter write, “The field of dark energy is very young and we may have a long and exciting period of exploration ahead before it matures.”
The December issue also includes reporting from Robert P Crease, historian at the Brookhaven National Laboratory, US, on the difficulty of deciding who should gain credit for the discovery of the accelerating universe and comment from Lawrence M Krauss, director of the Center for Education and Research in Cosmology and Astrophysics at Case Western Reserve University, US, on the possibility that we may never be able to tell if dark energy is a cosmological constant or something more exotic still.

Source: Physics World

Better membranes for water treatment

Researchers at the University of Illinois have developed a new generation of biomimetic membranes for water treatment and drug delivery. The highly permeable and selective membranes are based on the incorporation of the functional water channel protein Aquaporin Z into a novel A-B-A triblock copolymer.

The experimental membranes, currently in the form of vesicles, show significantly higher water transport than existing reverse-osmosis membranes used in water purification and desalination. The researchers describe their membranes in a paper accepted for publication in the Proceedings of the National Academy of Sciences. The paper is to be published in PNAS Online Early Edition this week.

“We took a close look at how kidneys so efficiently transport water through a membrane with aquaporins, and then we found a way to duplicate that in a synthetic system,” said Manish Kumar, a graduate research assistant at the U. of I., and the paper’s lead author.

Unlike most biological membranes, polymer membranes are very stable and can withstand considerable pressure – essential requirements for water purification and desalination processes. “Placing aquaporins in materials that we can use outside the body opens doors to industrial and municipal applications,” Kumar said.

To make their protein-polymer membranes, the researchers begin with a polymer that self-assembles into hollow spheres called vesicles. While the polymer is assembling, the researchers add Aquaporin Z – a protein found in Escherichia coli bacteria.
“Aquaporin Z makes a hole in the membrane that only water can go through, so it’s both fast and selective,” said membrane specialist Mark Clark, a professor of civil and environmental engineering and one of the paper’s co-authors.

“By varying the amount of Aquaporin Z, we can vary the membrane’s permeability,” Kumar said, “which could be very useful for drug-delivery applications.”
With their high permeability and high selectivity, the biomimetic membranes also are ideal for water treatment by desalination, which is becoming increasingly important for water purification in semiarid coastal regions.

When tested, the productivity of the Aquaporin Z-incorporated polymer membranes was more than 10 times greater than other salt-rejecting polymeric membranes.
Currently, the experimental polymer membranes exist only as small vesicles. “Our next step is to convert the vesicles into larger, more practical membranes,” Kumar said. “We also want to optimize the membranes for maximum permeability.”

Source: Proceedings of the National Academy of Sciences

Youngest solar systems found

Astronomers at the University of Michigan have found what are believed to be some of the youngest solar systems yet detected.

The systems are around the young stars UX Tau A and LkCa 15, located in the Taurus star formation region just 450 light years away. Using a telescope that measures levels of infrared radiation, the researchers noticed gaps in the protoplanetary disks of gas and dust surrounding these stars. They say those gaps are most likely caused by infant planets sweeping those areas clear of debris.

A paper on the findings by astronomy doctoral student Catherine Espaillat, professor Nuria Calvet, and their colleagues is published in the Dec. 1 issue of Astrophysical Journal Letters.
"Previously, astronomers were seeing holes at the centers of protoplanetary disks and one of the theories was that the star could be photoevaporating that material," said Espaillat, first author of the paper.

Photoevaporation refers to the process of heating up the dust and gas in the surrounding cloud until it evaporates and dissipates. "We found that in some stars, including these two, instead of a hole, there's a gap," Espaillat said. "It's more like a lane has been cleared within the disk. That is not consistent with photoevaporation. The existence of planets is the most probable theory that can explain this structure."

The researchers used NASA's Spitzer Space Telescope for this study. The infrared orbiting telescope observes energy at wavelengths invisible to optical telescopes. That allowed astronomers to study these "pre-main sequence stars" in a deeper way.

A main sequence star is an average adult star, like the sun, which burns by converting hydrogen into helium. Pre-main sequence stars like UX Tau A and LkCa 15 haven't yet established this conversion process. They derive energy from gravitational contraction. UX Tau A and LkCa 15 are both about 1 million years old.

"They're baby stars," Calvet said. The sun, for comparison, is a middle-aged star at 4.5 billion years old. Calvet said this research adds new insights to the study of solar systems.
"We are looking for our history," Calvet said. "We are looking for the history of solar systems, trying to understand how they form."

Source: Astrophysical Journal Letters.

1.5 million books Online

International project makes complete texts available through single Web portal

The Million Book Project, an international venture led by Carnegie Mellon University in the United States, Zhejiang University in China, the Indian Institute of Science in India and the Library at Alexandria in Egypt, has completed the digitization of more than 1.5 million books, which are now available online.

For the first time since the project was initiated in 2002, all of the books, which range from Mark Twain’s “A Connecticut Yankee in King Arthur’s Court” to “The Analects of Confucius,” are available through a single Web portal of the Universal Library (www.ulib.org), said Gloriana St. Clair, Carnegie Mellon’s dean of libraries.

“Anyone who can get on the Internet now has access to a collection of books the size of a large university library,” said Raj Reddy, professor of computer science and robotics at Carnegie Mellon. “This project brings us closer to the ideal of the Universal Library: making all published works available to anyone, anytime, in any language. The economic barriers to the distribution of knowledge are falling,” said Reddy, who has spearheaded the Million Book Project.

Though Google, Microsoft and the Internet Archive all have launched major book digitization projects, the Million Book Project represents the world’s largest, university-based digital library of freely accessible books. At least half of its books are out of copyright, or were digitized with the permission of the copyright holders, so the complete texts are or eventually will be available free.

The collection includes a large number of rare and orphan books. More than 20 languages are represented among the 1.5 million books, a little more than 1 percent of all of the world’s books.

Many of the books, particularly those in Chinese and English, have been digitized — their text converted by optical character recognition methods into computer readable text. That allows these books to be searched and, eventually, reformatted for access by PDAs and other devices.

An outgrowth of Reddy’s Universal Library, the Million Book Project received $3.5 million in seed funding from the National Science Foundation and substantial in-kind contributions from hardware and software manufacturers. These funds were primarily used to purchase scanning equipment and for developing the scanning, digitization and cataloguing methods necessary for creating a large digital library.

The vast majority of the scanning, digitization and cataloguing has been performed at centers in China and India, where more than 1.1 million and 360,000 books have been scanned, respectively. The U.S., China and India provided $10 million each in cash and in-kind contributions to the project. More recently, the Library at Alexandria, Egypt, has joined the effort. Now, about 7,000 books are scanned daily by more than 1,000 workers worldwide.

“We greatly value the participation of Bibliotheca Alexandrina,” said Michael Shamos, a Carnegie Mellon computer science professor and copyright lawyer. “Scholars everywhere regret the destruction of the Alexandria Library at various points in history, and we’re willing to go to great lengths to see that no such destruction is ever possible in the future. Once books are on the Internet, they become immortal.”

Protecting and preserving texts is a major goal, said Pan Yunhe, the leader of the Million Book Project in China. “Paper gets old and brittle, so books soon become so delicate that no one can read them without damaging them,” said Yunhe, the former president of Zhejiang University who is now vice president of the Chinese Academy of Engineering. “Artwork fades. But once we have digitized texts and illustrations, we can keep them in circulation indefinitely. And by storing them at multiple sites, we can minimize the risk that they be destroyed, as occurred in Alexandria.”

“This collection of books in multiple languages opens up unparalleled opportunities to bring Indian cultural material to everyone, and offers a huge range of possibilities in natural language research,” said N. Balakrishnan, associate director of the Indian Institute of Science in Bangalore, one of the partners in the project.

“Digital libraries constitute an essential part of the future of the developing world,” said Ismail Serageldin, director of Bibliotheca Alexandrina. ”This requires that we approach conditions governing copyright, digital archiving and scientific databases with a view to creating two-tier systems of access to information that would allow access to such data from developing countries for a nominal fee or for free.”

Though the long-term goal of the Universal Library is to make books, artwork and other published works available online for free, about half of the current collection remains under copyright. Until the permission of the copyright holders can be documented, or copyright laws are amended, only 10 percent or less of those books can be accessed at no cost.

Source: Carnegie Mellon University

How our ancestors were like gorillas

Fossils illustrate sex differences in growth and the costs of being a male

Research published in this week’s Science journal shows that some of our closest extinct relatives had more in common with gorillas than previously thought. Dr Charles Lockwood, UCL Department of Anthropology and lead author of the study, said: “When we examined fossils from 1.5 to 2 million years ago we found that in one of our close relatives the males continued to grow well into adulthood, just as they do in gorillas. This resulted in a much bigger size difference between males and females than we see today.

“It’s common knowledge that boys mature later than girls, but in humans the difference is actually much less marked than in some other primates. Male gorillas continue to grow long after their wisdom teeth have come through, and they don't reach what is referred to as dominant "silverback" status until many years after the females have already started to have offspring. Our research makes us think that, in this fossil species, one older male was probably dominant in a troop of females. This situation was risky for the males and they suffered high rates of predation as a result of both their social structure and pattern of growth.”

The research used 35 fossilised specimens of Paranthropus robustus, an extinct relative of Homo sapiens which existed almost two million years ago. The fossils came from the palaeontological sites of Swartkrans, Drimolen and Kromdraii, all of which are in South Africa’s Cradle of Humankind World Heritage Site near Johannesburg.

The research was inspired by earlier discoveries at Drimolen by Dr Andre Keyser, one of the co-authors of the study. Dr Colin Menter, from the University of Johannesburg and co-director of current fieldwork at Drimolen, explains: “Discoveries at this site showed us that sex differences in Paranthropus robustus were greater than we had previously thought. While there are some specimens from Drimolen that are just as large and robust as those from other sites like Swartkrans, there is a complete female skull that is distinctly smaller than the other, well-preserved specimens of the species.”

Jacopo Moggi-Cecchi, based at the University of Florence and an expert on fossil teeth, participated in the study and says: "It takes large samples of fossils to ask questions about variation and growth, and it's really a tribute to fieldworkers such as Robert Broom and Bob Brain [who worked at Swartkrans] that this research could even take place. It's also an example of why we need to continue to look for fossils after we think we know what a species is – more specimens allow us to answer more interesting questions. Even isolated teeth can give us new insights into what variation means.”

Dr Lockwood adds: “The pattern of growth also gives a better understanding of who is male and who is female in this sample of skulls and it turns out that there are far more males in the fossil sample. Because fossils from the most prolific site, Swartkrans, are thought to have been deposited by predators such as leopards and hyenas, it appears that males were getting killed more often than females.

"Basically, males had a high-risk, high-return lifestyle in this species. They most likely left their birth groups at about the time they reached maturity, and it was a long time before they were mature enough to attract females and establish a new group. Some of them were killed by predators before they got the chance."

A final point made by the researchers is that not all fossil hominin samples show the same patterns, and it is quite possible that further work will reveal clear diversity in social structure between human ancestors, in the same way that one sees differences among apes such as chimpanzees, bonobos, gorillas, and orangutans. This research will help us to understand how human social structure evolved.

Source: Science

Blood stem cells fight invaders, study finds

No other stem cell is more thoroughly understood than the blood, or hematopoietic, stem cell. These occasional and rare cells, scattered sparingly throughout the marrow and capable of replenishing an entire blood system, have been the driving force behind successful bone marrow transplants for decades. Scientists, for the most part, have seen this as the hematopoietic stem cell’s (HSC) singular role: to remain in the bone marrow indefinitely and to replenish blood and immune system cells only when called upon.

New research from the lab of Harvard Medical School professor of pathology Ulrich von Andrian, published in the November 30 edition of Cell, now suggests that HSCs’ biological role is far more versatile and dynamic. He and his colleagues have found that HSCs can travel from the bone marrow, through the blood system, and enter visceral organs where they perform reconnaissance missions in search of pathogenic invaders. Upon encountering an invader they immediately synthesize a defense, divide and mature, churning out new immune system cells such as dendritic cells and other leukocytes, right on the spot.

“This process changes the way we look at blood stem cells,” says von Andrian.
For almost five decades scientists have known that a fraction of HSCs will sometimes migrate from the bone marrow into the bloodstream. And while scientists have observed this phenomenon, they haven’t known exactly why the stem cells would do this, and what sort of itinerary they might follow once they entered the blood. A group in von Andrian’s lab, led by postdoctoral researcher and cardiologist Steffen Massberg, decided to explore this question.

They began be extracting lymph samples from the thoracic duct of a mouse. The thoracic duct, a major component of the lymphatic system, routes the body’s excess fluids into the circulation, fluids that normally accumulate in organs. In that sense, it’s a kind of physiological storm drainage system. The group reasoned that any itinerary would eventually bring these cells into the lymph system, so it marked a logical starting point.

After screening large samples of thoracic fluid, they discovered an extremely small population of cells that, after rigorous testing, behaved identically to blood stem cells. Further tests, which involved mice genetically engineered so that their blood stem cells could be detected through fluorescent microscopy, revealed that these cells were also scattered throughout visceral organs, such as liver, heart, and lung.

“Taken all together, a picture developed suggesting that these cells migrated from the marrow and into the circulation where they would then leak out and enter the tissue,” says Massberg. “After that, the thoracic duct would empty them back into the circulation, where they could reenter the marrow. But the question was, why" What exactly are they doing"”

The group had found that the stem cells remain in the tissue for thirty-six hours before exiting into the thoracic duct. This suggested that they were conducting some kind of surveillance. To test this, Massberg and his colleagues injected a bacterial endotoxin into the mouse tissue. Within a matter of days, clusters of specialized immune cells formed in the infected areas.
“Typical immune responses deplete local specialized immune cells,” says Massberg. “It appears that the hematopoietic stem cells initiate an immune response and replenish these specialized immune cells. It’s a way of sensing local environmental disturbances and responding locally.”

But finally, the researchers identified the molecular mechanism that explained these observational data.

After residing for a while in the organ tissue, the stem cells receive a lipid signal that enables them to exit into the thoracic duct. However, the presence of endotoxin disrupts the normal signaling cascade. When the receptors on the stem-cell surface that detect the pathogens become active, the cell’s ability to receive the lipid signal is blocked. The stem cells literally get stuck in the tissue, where they are then triggered to proliferate into immune cells.
“That stem cells are actually a part of the immune system, rather than just giving rise to it, is a very provocative idea,” says von Andrian. “This opens up a number of new avenues for us to explore ways that our bodies fight pathogens.” The researchers are now looking at ways that other common diseases, like cancer, may exploit this process.

Source: Cell, Harvard Medical School

European forests expanding: study

Credit for forest expansion likely needed by EU to reach ambitious post-2012 goal of cutting greenhouse gas emission 20 percent by 2020 from 1990 levels

European Union countries likely require an old ally – Mother Nature and her forests – to meet an ambitious post-Kyoto goal for cutting greenhouse gas emissions 20% by 2020, according to new research.

The University of Helsinki study says that despite rising population and affluence, the EU can meet its obligations post-Kyoto (2012-2020). However, it will likely require more than energy savings, new technologies and mitigating non-CO2 gasses such as methane; partial credit for expansion of the region’s forests could be decisive, say researchers Pekka E. Kauppi, Laura Saikku and Aapo Rautiainen, whose report, The Sustainability Challenge of Meeting Carbon Dioxide Targets in Europe by 2020, is published today in the peer-reviewed UK journal Energy Policy.

The study finds that between 1990 and 2005, expansion of above-ground tree vegetation in the 27 EU countries annually absorbed an additional 126 teragrams (126 million tonnes) of carbon – equal to 11% of the region’s emissions.

The rate varied from 10% in the 15 old member states (Austria, Belgium, Denmark, Finland, France , Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Portugal, Spain, Sweden, UK) to 15% in the 12 new members (Bulgaria, Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, Romania, Slovakia, Slovenia).

The findings were surprising, says study leader Prof. Kauppi, who with colleagues in 1992 estimated the rate of increase of CO2 absorbsion through the expansion of forests at no more than 5%.

The study shows that total CO2 sequestered by EU forests relative to national emissions varies widely from country to country. In Latvia, for example, forests more than offset per capita emissions. And forests in Lithuania, Sweden, Slovenia, Bulgaria and Finland absorb a large part of national emissions. At the other end of the scale are lightly-forested countries such as Belgium, Ireland, the Netherlands, Cyprus and Denmark.

The new paper builds on work reported last year by Prof. Kauppi and international collaborators, who revealed the shift from deforestation to afforestation in the world’s most forested nations. They advanced a more sophisticated approach to measuring forest cover that considers not just forested area but density of trees per hectare.

Their “Forest Identity” calculation also quantifies the biomass and atmospheric carbon stored in forests. They reported that, amid widespread concern about deforestation, growing stock has in fact expanded over the past 15 years in 22 of the 50 countries with most forest, including several EU members.

“The good news is that trees are extremely efficient mechanisms for capturing and storing carbon,” says Prof. Kauppi, a member of the Nobel-laureate UN International Panel on Climate Change. “The better news is that Europe’s forests are thriving and expanding and therefore will play an increasingly important role in helping the EU to reach its environmental goals.”

“Every year, the expanding European forests remove a surprisingly large amount of carbon from the atmosphere,” says co-author Aapo Rautiainen. “According to rough estimates, their impact in reducing atmospheric carbon may well be twice that achieved by the use of renewable energy in Europe today.”

Under the Kyoto Protocol, the EU commited to an 8% reduction of annual greenhouse gas emissions by 2012, using 1990 as the base year. Under the protocol, countries do not get credit for increasing natural carbon sinks through forestry and agriculture. Negotiations on an accord to cover the post-Kyoto period 2012 to 2020 are underway.

The researchers note the daunting challenge confronting EU nations in order to meet a post-Kyoto commitment to reduce emissions 20% from 1990 levels by 2020: a dramatic reduction of energy used per unit of GDP and de-carbonization of energy supply against a backdrop of rising population and affluence.

CO2 emissions in EU nations grew by an average of roughly 1% every three years between 1992 and 2004. To reduce CO2 emissions in EU27 by 20% in the next 12 years, carbon emission per economic output needs to at least halved (49 to 64% depending on the growth of population and economy).

The report’s authors note that Europe-wide emissions have not yet started to decline and that time is running out for the EU to successfully embark on it ambitious 2020 goal.
“Policies that accelerate the expansion of our forest biomass not only represent a win-win for climate change and biodiversity, they also open up economic opportunities,” says co-author Laura Saikku. “Land owners can benefit with new industries like forest-based bio-energy production. This could also help to reduce one of the main threats to sustained forest expansion – the need to open land to produce agricultural biofuels as alternatives to fossil fuels.”
Source: Energy Policy

Light Show on Venus

Venus is a hellish place of high temperatures and crushing air pressure. The European Space Agency's Venus Express mission adds into this mix the first confirmation that the Venusian atmosphere generates its own lightning. The discovery is part of the Venus Express science findings that appear in a special section of the Nov. 29 issue of the journal Nature.

"In addition to all the pressure and heat, we can confirm there is lightning on Venus -- maybe even more activity than there is here on Earth," said Christopher Russell, a NASA-sponsored scientist on Venus Express from the University of California, Los Angeles, and lead author of one of the Nature papers. "Not a very good place to vacation, that is for sure."

The discovery puts Venus in elite planetary company. Scientists currently know of only three other planetary bodies in the entire universe that generate lightning -- Earth, Jupiter and Saturn. Lightning on Venus -- as well as on any other planet -- is an important discovery because the electrical discharges drive the chemistry of an atmosphere by breaking molecules into fragments that can then join with other fragments in unexpected ways.

The lightning on Venus is unique from that found on Earth, Jupiter and Saturn in that it is the only lightning known that is not associated with water clouds. Instead, on Venus, the lightning is associated with clouds of sulfuric acid. Any future missions to the second rock from the sun may have to take into account the electrical activity in the Venusian atmosphere. The confirming measurements of the electrical discharges were made with data obtained by the Venus Express magnetometer instrument provided by the Space Research Institute in Graz, Austria.

The measurements were taken once a day for two minutes, during a period when the spacecraft was closest to Venus. A Venusian day is about 117 days long. With its primary mission completed, Venus Express will now embark upon its extended mission to watch Earth's nearest planetary neighbor for two more Venusian days. Among other things, it will look for the telltale infrared radiation from lava flows.

In 2010, when a Japanese mission, Venus Climate Orbiter, also called Planet-C, arrives at Venus, scientists will be able to compare results from the two spacecraft. More than 250 scientists and engineers across Europe are involved in the Venus Express mission, supported by their institutes and national space agencies. The mission also sees the contribution of scientists from Russia and Japan, as well as from NASA, which sponsors 15 American Venus Express scientists and provides support to the radio science investigation via its Deep Space Network antennas.

Source: Jet Propulsion Laboratory, Pasadena

Old Dwarf Galaxy with a Juvenescent Heart

Using the 8.2 meter Subaru Telescope on the summit of Mauna Kea, an observing team of 15 Japanese astronomers conducted a thorough inspection of a galaxy building block. They found that a small galaxy named Leo II largely consists of older stars, a sign of survival through galactic cannibalism under which massive galaxies (i.e. Milky Way) consume smaller galaxies to attain their extensive size. Researchers also found younger stars in the galactic center of Leo II.

Leo II is categorized as a spheroidal dwarf galaxy that resides approximately 760,000 light years away from our Milky Way. Even though this is one of the galaxies closest to us, it is very faint, small, and difficult to make detailed observations. The astronomers used the 80-megapixel Suprime-Cam camera on the Subaru Telescope to conduct their research because its wide-field coverage and good image quality are ideal for investigating stellar contents of such galaxies.

Over 2 nights, 90 minutes of exposures were taken and 82,252 stars were detected down to a visible magnitude of 26 (the human eye cannot see below magnitude 6). The group reported that the data set contained excellent results providing critical information on the properties of the stars within Leo II.The scientists found red giant stars throughout Leo II, toward the center as well as the outer areas. The results further showed that the stars in the outer portions of the galaxy are metal deficient, that is, older than towards the inner areas.

In addition, observations identified some remnant of globular clusters towards the eastern edge of Leo II that may have experienced tidal disruption; their violent history is yet to be explained. The astronomers concluded that major star formation occurred at a modest rate in Leo II about 8 billion years ago, and that star formation started from the outside toward the center stopping approximately 4 billion years ago, except for the very center of the galaxy where younger stars are found. On Wednesday, November 28, 2007, Dr. Yutaka Komiyama presented the results on the web.

Source: Subaru Telescope Facility, Hawaii

Malaria parasite's distinct physiological states

Novel states, not seen in lab cell cultures, may be linked to variable course of disease; Insight flows from unique approaches to analyzing genomic data

The malaria parasite has been studied for decades, but surprisingly, little is known about how it behaves in humans to cause disease. In a groundbreaking study published November 28 in the advance online edition of Nature, an international research team has for the first time measured which of the parasite's genes are turned on or off during actual infection in humans, not in cell cultures, unearthing surprising behaviors and opening a window on the most critical aspects of parasite biology.

That insight springs from the genomic analysis of parasites in their natural state, derived directly from patients residing in Senegal, and also from the researchers' use of innovative computational approaches to interpret their results. These computational methods helped to identify three distinct biological states of the malaria parasite: an active growth-based state, a starvation response and an environmental stress response, presumably related to the body's inflammatory response to the parasite. This physiological diversity was previously unknown and may help explain the widely varying course of the disease in different patients, from mild, flu-like illness to coma and even death.

"For the first time, we have glimpsed the biology of the malaria parasite in one of its most important environments -- humans," said co-senior author Aviv Regev, a core member of the Broad Institute of MIT and Harvard and an assistant professor of biology at MIT. "Our unique computational approach holds promise not only for understanding the malaria pathogen, but likely other important microbes as well."

"This work illustrates the true power that comes from developing the right computational methods and applying them to important biomedical problems," said co-senior author Jill Mesirov, director of Computational Biology and Bioinformatics at the Broad Institute of MIT and Harvard. "Even more importantly, it reflects scientific research at its best -- a global effort that brings together clinicians and researchers with diverse expertise, working directly with patients in areas hardest hit by disease."

In its natural state, the malaria parasite, Plasmodium falciparum, leads a complicated life. It proceeds through a series of distinct developmental stages both in humans and in mosquitoes, the main vector for disease transmission. Malaria researchers typically circumvent this complexity by studying the parasite in cultured cells. Yet in this artificial setting, few differences have been found in the genes that are turned on or off in various strains of P. falciparum. That uniformity is surprising, because it fails to explain the drastically different courses experienced by malaria patients.

To explore the basis for these differences, first author Johanna Daily, an infectious disease physician at Brigham and Women's Hospital, assistant professor of medicine at Harvard Medical School, and a researcher at both the Harvard School of Public Health and the Broad Institute, set out to observe P. falciparum in its natural environment: the human circulation. Using small samples of blood collected from more than 40 malaria patients in Senegal, Daily and her colleagues worked meticulously to devise a method for isolating genetic material from parasites, allowing them to determine which of the nearly 6,000 P. falciparum genes are switched on or off during infection in humans. Importantly, all of the patients involved in the study harbored similar-looking parasites, yet their symptoms varied widely.

These clinical research efforts were led by Professor Souleymane Mboup and Dr. Daouda Ndiaye at Cheikh Anta Diop University. "This project would not have been possible without the dedicated work of our collaborators in Senegal," said co-author Dyann Wirth, a professor and chairman of the department of immunology and infectious diseases at the Harvard School of Public Health and the co-director of the Broad Institute's Infectious Disease Initiative. "We are grateful to them and to the many malaria patients who generously volunteered to participate in this study."

From the parasites in patients' blood, the researchers simultaneously measured the activity level, or "expression", of every P. falciparum gene. Co-author Elizabeth Winzeler, an associate professor at The Scripps Research Institute, led this aspect of the study. "The ability to look across the parasite's entire genome was essential," said Winzeler. "We uncovered extraordinary things about parasite biology -- things we could not have even imagined."
Winzeler, who is also head of malaria research at the Genomics Institute of the Novartis Research Foundation (GNF), where much of the genomic work was performed, is grateful that organizations like GNF choose to encourage these types of high-risk studies. "We are especially excited about using these observations to guide our drug discovery efforts," she said.

The key to interpreting these results lay in two computational tools, first developed by Mesirov and her colleagues to study the genomics of human cancer cells. By adapting these tools for malaria, the researchers were able to identify distinct groups of parasites, each marked by characteristic sets of active and inactive genes. The biological underpinnings of these groups were made clearer through a second innovative approach: systematically comparing P. falciparum -- whose genes and genome are poorly understood -- to the baker's yeast, an organism that has been extensively characterized at the genetic level. Since the malaria parasite and the baker's yeast are both single-celled eukaryotes, it is possible they may share some of the same cellular machinery and could also respond in some similar ways to their surroundings.

With this unusual approach, co-senior author Regev and her colleagues were able to describe three different classes of parasites, one of which displayed features associated with a well-known form of parasite metabolism. The other groups, however, were very unusual, reflecting modes of parasite behavior that had never before been described.
One of these novel groups seems to signal parasites that are under extreme environmental stress. Importantly, this group shows a clear correlation with patient symptoms, including high fevers and elevated levels of inflammatory markers in the blood. "This is a remarkable result -- it suggests the malaria parasite can sense what is happening within its host and adjust its biology accordingly," said Daily. "That interaction signals a fundamental shift in the way we think about malaria, one which will hopefully lead to more effective treatments -- particularly for the most severe cases of the disease."

The other parasite group is associated with an alternative form of parasite metabolism, which relies on two specialized cellular compartments called the mitochondria and the apicoplast. That result is particularly surprising since mitochondria in P. falciparum were previously thought to be non-functional. "For decades, our knowledge of the parasite has been driven solely by studies in cultured cells, not in humans," said Wirth. "Our work underscores the importance of studying the malaria parasite in its natural environment and will hopefully spark novel approaches to malaria drug discovery."

Source: Nature, Broad Institute of MIT and Harvard

SIRT1 activators for treating diseases of aging

Therapeutic type 2 diabetes data published in the journal Nature

Sirtris Pharmaceuticals, Inc. (NASDAQ: SIRT), a biopharmaceutical company focused on discovering and developing small molecule drugs to treat diseases of aging, announced today that findings in the journal Nature demonstrate that Sirtris has developed novel drug candidates that offer a promising, new approach to treating diseases of aging, including Type 2 Diabetes, by targeting SIRT1, a gene that controls the aging process.

In November 2006, Sirtris scientists and Sirtris co-founder, Prof. David Sinclair from Harvard Medical School, published consecutive papers in the journals Cell and Nature showing that resveratrol, a SIRT1 activator found in red wine, could reduce the impact of a high fat diet, increase stamina two fold and significantly extend lifespan of mice. Unfortunately, it was estimated that a person would need to drink 1000 bottles of red wine to obtain an equivalent dose of resveratrol. Now, scientists at Sirtris have developed SIRT1 activating molecules that are chemically distinct from resveratrol and are 1000 times more potent.

"The new drug candidates represent a significant milestone because they are the first molecules that have been designed to act on genes that control the aging process. For this reason, we feel they have considerable potential to treat diseases of aging such as Type 2 Diabetes," said Christoph Westphal, M.D., Ph.D., Chief Executive Officer and Vice Chair of Sirtris Pharmaceuticals. "The breakthrough in potency we have achieved with the novel chemical entities (NCEs) means that we can obtain the health benefits of resveratrol with a considerably lower dose."

The Nature paper from Sirtris shows that in diet-induced obese and genetically obese mice, Sirtris’ small molecule NCEs improve insulin sensitivity, lower plasma glucose levels and increase the function of mitochondria (the powerhouses of all cells). In another well-established preclinical model of Type 2 Diabetes and insulin resistance (Zucker fa/fa rats), these SIRT1 activators improved whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. These rodent models of diabetes are considered highly predictive of efficacy in humans.

The World Health Organization (WHO) indicates that Type 2 Diabetes (formerly called adult-onset diabetes) results from the body’s ineffective use of insulin. Type 2 Diabetes accounts for 90% of diabetes around the world, and is largely the result of excess body weight and physical inactivity. WHO estimates that more than 180 million people worldwide have diabetes and this number is likely to more than double by 2030. Furthermore, WHO projects that deaths due to diabetes will increase by more than 50% in the next 10 years. Activating SIRT 1 appears to mimic the beneficial effects of calorie restriction on mitochondrial and metabolic function in mammals in vivo and holds promise for treating diseases of aging, such as Type 2 Diabetes.

"We are very excited about these findings, which expand on the breakthrough data published in 2006 in the journals Nature and Cell, which demonstrated that SIRT1 activators mimic calorie restriction and extend lifespan. For the first time, the article published today shows that the novel drug candidates we have identified are the most potent SIRT1 activators ever to be published -- 1,000 times more potent than resveratrol -- and can potentially unlock a whole new approach to treating Type 2 Diabetes," stated Jill C. Milne, Ph.D., lead author of the Nature study and Senior Director of Biology at Sirtris.

Westphal added, “Now we have an even more potent way of eliciting the beneficial effects observed in earlier research with resveratrol. The NCEs characterized in this study are significantly more potent than and structurally unrelated to resveratrol. These findings highlight the tremendous potential of our NCE program to treat diseases of aging, and we look forward to advancing one of these promising new compounds into human clinical studies in the first half of 2008.”

Sirtuins are a recently-discovered family of enzymes that promote the body's natural defense against disease. There are seven human sirtuins (SIRT1-7). Sirtuins are attractive drug targets because some have a specialized function in mitochondrial activity which may be therapeutically beneficial for metabolic and other diseases of aging. Sirtuin therapeutics offer the potential for a novel class of drugs that can treat diseases of aging in a new way.

Source: Nature

High blood pressure may heighten effects of Alzheimer's disease

Having hypertension, or high blood pressure, reduces blood flow in the brains of adults with Alzheimer’s disease, according to a new study presented today at the annual meeting of the Radiological Society of North America (RSNA).

“While hypertension is not a cause of Alzheimer’s disease, our study shows that it is another hit on the brain that increases its vulnerability to the effects of the disease,” said study co-author Cyrus Raji, scientist and M.D. and Ph.D. candidate at the University of Pittsburgh where the study was conducted.

Hypertension is a condition in which the blood circulates through the arteries with too much force. According to the National Heart, Lung and Blood Institute, approximately 50 million Americans have hypertension. People with hypertension are at elevated risk for heart attack, stroke and aneurysm. Recently, there has been mounting evidence tying cardiovascular health to brain health.

“This study demonstrates that good vascular health is also good for the brain,” said co-author Oscar Lopez, M.D., professor of neurology and psychiatry at the University of Pittsburgh. “Even in people with Alzheimer’s disease, it is important to detect and aggressively treat hypertension and also to focus on disease prevention.”

For the study, the researchers used arterial spin-labeled magnetic resonance imaging (MRI), which can measure blood flow in the brain, to image 68 older adults. Arterial spin-labeled MRI is a novel, noninvasive technique that requires no external contrast agent.

The patient group included 48 normal individuals, including 38 with hypertension and 10 without; 20 Alzheimer’s patients, including 10 with hypertension and 10 without; and 20 adults with mild cognitive impairment, 10 with hypertension and 10 without. Mild cognitive impairment, which affects brain functions such as language, attention and reasoning, is a transition stage between normal aging deficits in the brain and greater levels of dementia.

The MRI results showed that in all patient groups blood flow in the brain was substantially decreased in patients with hypertension compared to those without. Cerebral blood flow was lowest among the Alzheimer’s patients with hypertension, but the normal group with hypertension showed significantly lower cerebral blood flow than the normal group without hypertension.

“These results suggest that by changing blood flow to the brain, hypertension—treated or untreated—may contribute to the pathology of Alzheimer’s,” Raji said.

Source: Radiological Society of North America