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Thursday, 29 December 2011

For every road there is a tire

Life is complicated enough, so you can forgive the pioneers of DNA biology for glossing over transcriptional elongation control by RNA polymerase II, the quick and seemingly bulletproof penultimate step in the process that copies the information encoded in our DNA into protein-making instructions carried by messenger RNA. In a new report appearing in the Dec. 23, 2011, issue of Molecular Cell, researchers at the Stowers Institute for Medical Research add not just a new layer, but a whole new dimension to transcriptional elongation control with evidence that for each class of genes transcribed by RNA polymerase II (Pol II), there exists a specific class of elongation factors.

The Stowers team, led by investigator Ali Shilatifard, Ph.D., discovered that ELL, short for eleven-nineteen lysine-rich leukemia, not only belongs to an assemblage of transcription elongation factors, which Shilatifard's lab had identified as the "Super Elongation Complex" (SEC) a few years ago, but also that ELL is part of a distinct "Little Elongation Complex" (LEC), which acts on a completely different class of genes transcribed by Pol II. Their findings illustrate that the elongation stage of transcription is a much more specific regulator of gene expression than previously believed.

"About fifteen years ago, transcriptional elongation control was not considered all that important for the regulation of gene expression," says Shilatifard of the standard biology textbook descriptions of RNA transcription, which assume that the molecular machinery that supported transcription elongation was one-size-fits-all. "Once RNA polymerase II departed from the promoter regions, it didn't matter all that much what happened next," he says.

Transcriptional elongation is the step following promoter clearance and the step before termination, and was considered to be largely unregulated. The old metaphor was a train running on tracks. "Polymerase is the train. It sat at the promoter -- which would correspond to the station," Shilatifard explains. "The polymerase train would leave the promoter/station and before long would arrive at the end of the gene. The process of the train traveling between the station and the endpoint of the gene -- is considered elongation."

The latest findings derail the train metaphor. "We have shown that there are specific classes of elongation factors for different classes of genes. Therefore, much more is involved than a train simply following a predestined track," he says. "Years ago, B.F. Goodrich (the tire company) advertised that, 'for every road, there is a tire'. What we are learning is that for every class of genes, there seems to be a specific class of elongation factors. The specificity of the complexes seems to control which classes of genes are transcriptionally regulated," says Shilatifard.

Edwin Smith, Ph.D., a research scientist in Shilatifard's lab, identified LEC in Drosophila cells while biochemically dissecting the proteins associated with theDrosophila homolog of the ELL protein. In human cells, where ELL is found within the SEC, it is required to induce the expression of a class of genes specific for the pathogenesis of a subtype of genes involved in acute leukemia.

This type of leukemia results when, through a process known as translocation, the mixed lineage leukemia (MLL) gene becomes fused to any of a number of seemingly unrelated genes. In earlier studies, Shilatifard's group found that many of MLL's fusion partners, including ELL, belong to the SEC. When MLL fuses with any of these unrelated partners, the whole SEC, much like an entourage, now follows MLL to its normal target genes misregulating their elongation and ultimately causing leukemia.

While humans have three ELL genes, fruit flies have only one ELL, but its structural similarity to the human ELLs suggested an evolutionarily conserved and vital function. To find out more about ELL's function in both creatures, Smith searched forDrosophila interaction partners in collaboration with Michael Washburn, Ph.D., and Laurence Florens, Ph.D., who head proteomics at the Stowers. They used their multi-dimensional protein identification technology, or MudPIT, to identify a set of relatively uncharacterized proteins in Drosophila that associate with the C-terminus of ELL in a complex the Shilatifard lab named the "Little Elongation Complex" or LEC.

When Smith knocked down LEC subunits in fruit flies and analyzed the global expression pattern defect with Alexander Garrett, Ph.D., a bioinformatician in the Shilatifard lab, they found that the expression levels of small nuclear RNA (snRNA) genes plummeted. Unlike other RNAs transcribed by RNA pol II, these snRNA molecules are not translated into proteins, instead they team up with proteins to form small nuclear ribonucleoproteins (snRNPs) known by the cheerful name of "snurps." They form the spliceosome, which edits messenger RNA after it is transcribed from DNA. Smith, Garrett, and Chengqi Lin, a graduate student in Shilatifard's laboratory, also demonstrated that this function of LEC is highly conserved from Drosophila to mammals.

"The specialization of the SEC and LEC complexes for mRNA and snRNA-containing genes, respectively, suggests the presence of specific classes of elongation factors for each class of genes transcribed by RNA polymerase II, which is of fundamental significance," says Smith.

"The next step is to figure out what other classes of genes use other classes of elongation factors. And what are the differential mechanisms of recruitment to RNA Polymerase II on different classes of genes? Once we get a handle on these distinct classes of genes, we hope to be able to modify different classes of genes by modifying these elongation factors." This would be new perspective regarding basic biology and clinical intervention, Shilatifard believes.

Genetic study of black chickens shed light on mechanisms causing rapid evolution in domestic animals

The genetic changes underlying the evolution of new species are still poorly understood. Genetic studies in domestic animals can shed light on this process due to the rapid evolution they have undergone over the last 10,000 years. A new study describes how a complex genomic rearrangement causes a fascinating phenotype in chickens. In the study published in PLoS Genetics researchers at Uppsala University, Swedish University of Agricultural Sciences, North Carolina State University and National Chung-Hsing University have investigated the genetic basis of fibromelanosis, a breed characteristic of the Chinese Silkie chicken (image on left). This trait involves a massive expansion of pigment cells that not only makes the skin and comb black but also causes black internal organs. Chickens similar in appearance to the Silkie were described by Marco Polo when he visited China in the 13th century and Silkie chickens have a long history in Chinese cuisine and traditional Chinese medicine.

"We have shown that the genetic change causing fibromelanosis is a complex rearrangement that leads to increased expression of Endothelin 3, a gene which is known for promoting the growth of pigment cells," explains Ben Dorshorst the post-doctoral researcher responsible for the work.

The research group led by Leif Andersson has by now characterized a number of traits in domestic animals, and a clear trend is emerging, namely that genomic rearrangements have contributed significantly to the rapid evolution of domestic animals. Other examples include Greying with age in horses and mutations affecting the size and shape of the comb in chickens.

"We have good reason to believe that such rearrangements have also played a significant role in the evolution of other species, including ourselves," concludes Leif Andersson.

The researchers also studied other chicken breeds where fibromelanosis occurs, including the Bohuslän-Dals svarthöna breed (image on right) from Sweden, and they found that all fibromelanotic breeds carried the exact same very unusual mutation. This finding is consistent with anecdotal evidence suggesting that this Swedish breed of chicken inherited their black skin and internal connective tissue color from Asian chickens that were first brought to Norway by a sailor on the East Asian trade routes centuries ago. This is a nice example of how humans have distributed a single novel mutation with an interesting effect when they developed breeds of domestic animals around the world. -- It is obvious that humans have had a strong affection for biological diversity in their domestic animals, says Leif Andersson.

How bacteria fight flouride

Yale researchers have uncovered the molecular tricks used by bacteria to fight the effects of fluoride, which is commonly used in toothpaste and mouthwash to combat tooth decay. In the Dec. 22 online issue of the journal Science Express, the researchers report that sections of RNA messages called riboswitches -- which control the expression of genes -- detect the build-up of fluoride and activate the defenses of bacteria, including those that contribute to tooth decay.

"These riboswitches are detectors made specifically to see fluoride," said Ronald Breaker, the Henry Ford II Professor and chair of the Department of Molecular, Cellular and Developmental Biology and senior author of the study.

Fluoride in over-the-counter and prescription toothpastes is widely credited with the large reduction in dental cavities seen since these products were made available beginning in the 1950s. This effect is largely caused by fluoride bonding to the enamel of our teeth, which hardens them against the acids produced by bacteria in our mouths. However, it has been known for many decades that fluoride at high concentrations also is toxic to bacteria, causing some researchers to propose that this antibacterial activity also may help prevent cavities.

The riboswitches work to counteract fluoride's effect on bacteria. "If fluoride builds up to toxic levels in the cell, a fluoride riboswitch grabs the fluoride and then turns on genes that can overcome its effects," said Breaker.

Since both fluoride and some RNA sensor molecules are negatively charged, they should not be able to bind, he notes.

"We were stunned when we uncovered fluoride-sensing riboswitches" said Breaker. "Scientists would argue that RNA is the worst molecule to use as a sensor for fluoride, and yet we have found more than 2000 of these strange RNAs in many organisms."

By tracking fluoride riboswitches in numerous species, the research team concluded that these RNAs are ancient -- meaning many organisms have had to overcome toxic levels of fluoride throughout their history. Organisms from at least two branches of the tree of life are using fluoride riboswitches, and the proteins used to combat fluoride toxicity are present in many species from all three branches.

"Cells have had to contend with fluoride toxicity for billions of years, and so they have evolved precise sensors and defense mechanisms to do battle with this ion," said Breaker, who is also an investigator with the Howard Hughes Medical Institute. Now that these sensors and defense mechanisms are known, Breaker said, it may be possible to manipulate these mechanisms and make fluoride even more toxic to bacteria. Fluoride riboswitches and proteins common in bacteria are lacking in humans, and so these fluoride defense systems could be targeted by drugs. For example, the Yale team discovered protein channels that flush fluoride out of cells. Blocking these channels with another molecule would cause fluoride to accumulate in bacteria, making it more effective as a cavity fighter.

Fluoride is the 13th most common element in Earth's crust, and it is naturally present in high concentrations throughout the United States and elsewhere. Its use in toothpaste and its addition to city water supplies across the United States sparked a controversy 60 years ago, and the dispute continues to this day. In the United Kingdom, and in other European Union countries, fluoride is used to a much lesser extent due to fierce public opposition.

The new findings from Yale only reveal how microbes overcome fluoride toxicity. The means by which humans contend with high fluoride levels remains unknown, Breaker notes. He adds that the use of fluoride has had clear benefits for dental health and that these new findings do not indicate that fluoride is unsafe as currently used.

Millipede border control better than ours

A mysterious line where two millipede species meet has been mapped in northwest Tasmania, Australia. Both species are common in their respective ranges, but the two millipedes cross very little into each other's territory. The 'mixing zone' where they meet is about 230 km long and less than 100 m wide where carefully studied. The mapping was done over a two-year period by Dr Bob Mesibov, who is a millipede specialist and a research associate at the Queen Victoria Museum and Art Gallery in Launceston, Tasmania. His results have been published in the open access journal ZooKeys.

'I have no idea why the line is so sharp', said Dr Mesibov. 'The boundary runs up and down hills, crosses rivers and different bedrocks and soils, and ignores vegetation type and climate differences. Its position and its sharpness seem to be the result of an unexplained biological arrangement between the two millipede species.'

Biogeographers use the term 'parapatry' for the case where two species ranges meet but do not overlap, or overlap very little. Dr Mesibov said that parapatry has been reported before in other species of millipedes and in other terrestrial invertebrate animals, in Tasmania and elsewhere in the world. However, parapatric boundaries often parallel a geographical feature, such as a ridgeline, or a steep rainfall gradient.

'There does not seem to be an ecological or a geographic explanation for this particular boundary, or for any part of it. It is also longer than any other parapatric boundary I know about. At 230 km, it is 50% longer than the boundary between England and Scotland, and the 'border control' is a lot better than what we humans can do.'

The two millipede species, Tasmaniosoma compitale and T. hickmanorum, are in the same genus and thought to be closely related. They were first scientifically described in 2010, by the same author and again in ZooKeys. The parapatric boundary was mapped as a background study for later investigations of speciation in this group of millipedes, and of the mechanism of parapatry.

MSU chemists become the first to solve an 84-year-old theory

The same principle that causes figure skaters to spin faster as they draw their arms into their bodies has now been used by Michigan State University researchers to understand how molecules move energy around following the absorption of light. Conservation of angular momentum is a fundamental property of nature, one that astronomers use to detect the presence of satellites circling distant planets. In 1927, it was proposed that this principle should apply to chemical reactions, but a clear demonstration has never been achieved.

In the current issue of Science, MSU chemist Jim McCusker demonstrates for the first time the effect is real and also suggests how scientists could use it to control and predict chemical reaction pathways in general.

"The idea has floated around for decades and has been implicitly invoked in a variety of contexts, but no one had ever come up with a chemical system that could demonstrate whether or not the underlying concept was valid," McCusker said. "Our result not only validates the idea, but it really allows us to start thinking about chemical reactions from an entirely different perspective."

The experiment involved the preparation of two closely related molecules that were specifically designed to undergo a chemical reaction known as fluorescence resonance energy transfer, or FRET. Upon absorption of light, the system is predisposed to transfer that energy from one part of the molecule to another.

McCusker's team changed the identity of one of the atoms in the molecule from chromium to cobalt. This altered the molecule's properties and shut down the reaction. The absence of any detectable energy transfer in the cobalt-containing compound confirmed the hypothesis.

"What we have successfully conducted is a proof-of-principle experiment," McCusker said. "One can easily imagine employing these ideas to other chemical processes, and we're actually exploring some of these avenues in my group right now."

The researchers believe their results could impact a variety of fields including molecular electronics, biology and energy science through the development of new types of chemical reactions.

Dong Guo, a postdoctoral researcher, and Troy Knight, former graduate student and now research scientist at Dow Chemical, were part of McCusker's team. Funding was provided by the National Science Foundation.

New device could bring optical information processing

Researchers have created a new type of optical device small enough to fit millions on a computer chip that could lead to faster, more powerful information processing and supercomputers. The "passive optical diode" is made from two tiny silicon rings measuring 10 microns in diameter, or about one-tenth the width of a human hair. Unlike other optical diodes, it does not require external assistance to transmit signals and can be readily integrated into computer chips.

The diode is capable of "nonreciprocal transmission," meaning it transmits signals in only one direction, making it capable of information processing, said Minghao Qi (pronounced Chee), an associate professor of electrical and computer engineering at Purdue University.

"This one-way transmission is the most fundamental part of a logic circuit, so our diodes open the door to optical information processing," said Qi, working with a team also led by Andrew Weiner, Purdue's Scifres Family Distinguished Professor of Electrical and Computer Engineering.

The diodes are described in a paper to be published online Dec. 22 in the journal Science. The paper was written by graduate students Li Fan, Jian Wang, Leo Varghese, Hao Shen and Ben Niu, research associate Yi Xuan, and Weiner and Qi.

Although fiberoptic cables are instrumental in transmitting large quantities of data across oceans and continents, information processing is slowed and the data are susceptible to cyberattack when optical signals must be translated into electronic signals for use in computers, and vice versa.

"This translation requires expensive equipment," Wang said. "What you'd rather be able to do is plug the fiber directly into computers with no translation needed, and then you get a lot of bandwidth and security."

Electronic diodes constitute critical junctions in transistors and help enable integrated circuits to switch on and off and to process information. The new optical diodes are compatible with industry manufacturing processes for complementary metal-oxide-semiconductors, or CMOS, used to produce computer chips, Fan said.

"These diodes are very compact, and they have other attributes that make them attractive as a potential component for future photonic information processing chips," she said.

The new optical diodes could make for faster and more secure information processing by eliminating the need for this translation. The devices, which are nearly ready for commercialization, also could lead to faster, more powerful supercomputers by using them to connect numerous processors together.

"The major factor limiting supercomputers today is the speed and bandwidth of communication between the individual superchips in the system," Varghese said. "Our optical diode may be a component in optical interconnect systems that could eliminate such a bottleneck."

Infrared light from a laser at telecommunication wavelength goes through an optical fiber and is guided by a microstructure called a waveguide. It then passes sequentially through two silicon rings and undergoes "nonlinear interaction" while inside the tiny rings. Depending on which ring the light enters first, it will either pass in the forward direction or be dissipated in the backward direction, making for one-way transmission. The rings can be tuned by heating them using a "microheater," which changes the wavelengths at which they transmit, making it possible to handle a broad frequency range.

Wednesday, 28 December 2011

New technique makes it easier to etch semiconductors

Creating semiconductor structures for high-end optoelectronic devices just got easier, thanks to University of Illinois researchers. The team developed a method to chemically etch patterned arrays in the semiconductor gallium arsenide, used in solar cells, lasers, light emitting diodes (LEDs), field effect transistors (FETs), capacitors and sensors. Led by electrical and computer engineering professor Xiuling Li, the researchers describe their technique in the journal Nano Letters.

A semiconductor's physical properties can vary depending on its structure, so semiconductor wafers are etched into structures that tune their electrical and optical properties and connectivity before they are assembled into chips.

Semiconductors are commonly etched with two techniques: "Wet" etching uses a chemical solution to erode the semiconductor in all directions, while "dry" etching uses a directed beam of ions to bombard the surface, carving out a directed pattern. Such patterns are required for high-aspect-ratio nanostructures, or tiny shapes that have a large ratio of height to width. High-aspect-ratio structures are essential to many high-end optoelectronic device applications.

While silicon is the most ubiquitous material in semiconductor devices, materials in the III-V (pronounced three-five) group are more efficient in optoelectronic applications, such as solar cells or lasers.

Unfortunately, these materials can be difficult to dry etch, as the high-energy ion blasts damage the semiconductor's surface. III-V semiconductors are especially susceptible to damage.

To address this problem, Li and her group turned to metal-assisted chemical etching (MacEtch), a wet-etching approach they had previously developed for silicon. Unlike other wet methods, MacEtch works in one direction, from the top down. It is faster and less expensive than many dry etch techniques, according to Li. Her group revisited the MacEtch technique, optimizing the chemical solution and reaction conditions for the III-V semiconductor gallium arsenide (GaAs).

The process has two steps. First, a thin film of metal is patterned on the GaAs surface. Then, the semiconductor with the metal pattern is immersed in the MacEtch chemical solution. The metal catalyzes the reaction so that only the areas touching metal are etched away, and high-aspect-ratio structures are formed as the metal sinks into the wafer. When the etching is done, the metal can be cleaned from the surface without damaging it.

"It is a big deal to be able to etch GaAs this way," Li said. "The realization of high-aspect-ratio III-V nanostructure arrays by wet etching can potentially transform the fabrication of semiconductor lasers where surface grating is currently fabricated by dry etching, which is expensive and causes surface damage."

To create metal film patterns on the GaAs surface, Li's team used a patterning technique pioneered by John Rogers, the Lee J. Flory-Founder Chair and a professor of materials science and engineering at the U. of I. Their research teams joined forces to optimize the method, called soft lithography, for chemical compatibility while protecting the GaAs surface. Soft lithography is applied to the whole semiconductor wafer, as opposed to small segments, creating patterns over large areas -- without expensive optical equipment.

"The combination of soft lithography and MacEtch make the perfect combination to produce large-area, high-aspect-ratio III-V nanostructures in a low-cost fashion," said Li, who is affiliated with the Micro and Nanotechnology Laboratory, the Frederick Seitz Materials Research Laboratory and the Beckman Institute for Advanced Science and Technology at the U. of I.

Next, the researchers hope to further optimize conditions for GaAs etching and establish parameters for MacEtch of other III-V semiconductors. Then, they hope to demonstrate device fabrication, including distributed Bragg reflector lasers and photonic crystals.

"MacEtch is a universal method as long as the right condition for deferential etching with and without metal can be found," Li said.

Penn scientists pioneer new method for watching proteins fold

A protein's function depends on both the chains of molecules it is made of and the way those chains are folded. And while figuring out the former is relatively easy, the latter represents a huge challenge with serious implications because many diseases are the result of misfolded proteins. Now, a team of chemists at the University of Pennsylvania has devised a way to watch proteins fold in "real-time," which could lead to a better understanding of protein folding and misfolding in general. The research was conducted by Feng Gai, professor in the Department of Chemistry in the School of Arts and Sciences, along with graduate students Arnaldo Serrano, also of Chemistry, and Robert Culik of the Department of Biochemistry and Molecular Biophysics at Penn's Perelman School of Medicine. They collaborated with Michelle R. Bunagan of the College of New Jersey's Department of Chemistry.

Their research was published in the international edition of the journal Angewandte Chemie, where it was featured on the cover and bestowed VIP (very important paper) status.

"One of the reasons that figuring out what happens when proteins fold is difficult is that we don't have the equivalent of a high-speed camera that can capture the process, " Gai said. "If the process were slow, we could take multiple 'pictures' over time and see the mechanism at work. Unfortunately, no one has this capability; the folding occurs faster than the blink of an eye."

Gai's team uses infrared spectroscopy -- a technique that measures how much light different parts of a molecule absorbs -- to analyze proteins' structure and how this changes. In this case, the researchers looked at a model protein known as Trp-cage with an infrared laser setup.

In this experiment, Gai's team used two lasers to study structural changes as a function of time. The first laser acts as the starting gun; by heating the molecule, it causes its structure to change. The second laser acts as the camera, following the motions of the protein's constituent amino acids.

"The protein is made of different groups of atoms, and the different groups can be thought of as springs," Gai said. "Each spring has a different frequency with which it moves back and forth, which is based on the mass of the atom on either end. If the mass is bigger, the spring oscillates slower. Our 'camera' can detect the speed of that motion and we can relate it to the atoms it is made of and how that segment of the protein chain moves."

Even in a simple protein like Trp-cage, however, there are many identical bonds, and the researchers need to be able to distinguish one from another in order to see which of them are moving while the protein folds. One strategy they used to get around this problem was to employ the molecular equivalent of a tracking device.

"We use an amino acid with a carbon isotope marker," Culik said. "If it's incorporated into the protein correctly, we'll know where it is."

With a single carbon atom of the Trp-cage slightly heavier than the others, the research team can use its signature to infer the position of the other atoms as they fold. The researchers could then "tune" the frequency of their laser to match different parts of the protein, allowing them to isolate them in their analyses.

Similar isotopes could be inserted in more complicated molecules, allowing their folds to also be viewed with infrared spectroscopy.

"This technique enhances our structural resolution. It allows us to see which part is moving," Gai said. "That would allow us to see exactly how a protein is misfolding in a disease, for example."

'Rare' brain disorder may be more common than thought, say Mayo Clinic scientists

A global team of neuroscientists, led by researchers at Mayo Clinic in Florida, has found the gene responsible for a brain disorder that may be much more common than once believed. In the Dec. 25 online issue of Nature Genetics, the researchers say they identified 14 different mutations in the gene CSF1R that lead to development of hereditary diffuse leukoencephalopathy with spheroids (HDLS). This is a devastating disorder of the brain's white matter that leads to death between ages 40 and 60. People who inherit the abnormal gene always develop HDLS. Until now, a definite diagnosis of HDLS required examination of brain tissue at biopsy or autopsy. The finding is important because the researchers suspect that HDLS is more common than once thought and a genetic diagnosis will now be possible without need for a brain biopsy or autopsy. According to the study's senior investigator, neurologist Zbigniew K. Wszolek, M.D., a significant number of people who tested positive for the abnormal gene in this study had been diagnosed with a wide range of other conditions. These individuals were related to a patient known to have HDLS, and so their genes were also examined.

"Because the symptoms of HDLS vary so widely -- everything from behavior and personality changes to seizures and movement problems -- these patients were misdiagnosed as having either schizophrenia, epilepsy, frontotemporal dementia, Parkinson's disease, multiple sclerosis, stroke, or other disorders," says Dr. Wszolek. "Many of these patients were therefore treated with drugs that offered only toxic side effects.

"Given this finding, we may soon have a blood test that can help doctors diagnose HDLS, and I predict we will find it is much more common than anyone could have imagined," he says.

Dr. Wszolek is internationally known for his long-term efforts to bring together researchers from around the world to help find cases of inherited brain disorders and discover their genetic roots.

Dr. Wszolek's interest in HDLS began when a severely disabled young woman came to see him in 2003 and mentioned that other members of her family were affected. The diagnosis of HDLS was made by his Mayo Clinic colleague, Dennis W. Dickson, M.D., who reviewed the autopsy findings of the patient's uncle, who had previously been misdiagnosed as multiple sclerosis, and subsequently, Dr. Wszolek's patient and her father. All members of the family had HDLS.

Dr. Dickson had identified other cases of HDLS from Florida, New York, Oregon and Kansas in the Mayo Clinic Florida brain bank and knew of a large kindred in Virginia with similar pathology, based upon a presentation at the annual meeting of the American Association of Neuropathologists. With concerted efforts, Dr. Wszolek and collaborators at University of Virginia were able to obtain DNA samples from the Virginia kindred. Dr. Wszolek also sought other cases, particularly those that had been reported in the neuropathology literature, and he was able to obtain samples from Norway, the United Kingdom, Germany and Canada, and other sites in the U.S. He and his team of investigators and collaborators have since published studies describing the clinical, pathologic and imaging characteristics of the disorder, and they have held five international meetings on HDLS.

In this study, which included 38 researchers from 12 institutions in five countries, the study's first author, Rosa Rademakers, Ph.D., led the effort to find the gene responsible for HDLS. Her laboratory studied DNA samples from 14 families in which at least one member was diagnosed with HDLS and compared these with samples from more than 2,000 disease-free participants. The gene was ultimately found using a combination of traditional genetic linkage studies and recently developed state-of-the art sequencing methods. Most family members studied -- who were found to have HDLS gene mutations -- were not diagnosed with the disease, but with something else, thus emphasizing the notion that HDLS is an underdiagnosed disorder.

The CSF1R protein is an important receptor in the brain that is primarily present in microglia, the immune cells of the brain. "We identified a different CSF1R mutation in every HDLS family that we studied," says Dr. Rademakers. "All mutations are located in the kinase domain of CSF1R, which is critical for its activity, suggesting that these mutations may lead to deficient microglia activity. How this leads to white matter pathology in HDLS patients is not yet understood, but we now have an important lead to study."

"With no other disease have we found so many affected families so quickly," says Dr. Wszolek. "That tells me this disease is not rare, but quite common." He adds, "It is fantastic that you can start an investigation with a single case and end up, with the help of many hands, in what we believe to be a world-class gene discovery."

The study was funded by a Mayo benefactor and the Mayo Foundation. Additionally, Mayo Clinic in Florida is a Morris K. Udall Parkinson's Disease Research Center of Excellence supported by the National Institute of Neurological Disorders and Stroke.

Severe congenital disorder successfully treated in a mouse model for the first time

Using a mouse model, Heidelberg University Hospital researchers have for the first time successfully treated a severe congenital disorder in which sugar metabolism is disturbed. The team headed by Prof. Christian Körner, group leader at the Center for Child and Adolescent Medicine, demonstrated that if female mice are given mannose with their drinking water prior to mating and during pregnancy, their offspring will develop normally even if they carry the genetic mutation for the congenital disorder. The team's outstanding work will contribute to better understanding of the molecular processes of this metabolic disease, along with the key stages in embryonic development, and may offer a therapeutic approach for the first time. The Heidelberg-based researchers also collaborated with colleagues working with Prof. Hermann-Josef Gröne of the German Cancer Research Center (DKFZ)'s Division of Cellular and Molecular Pathology in Heidelberg. Their results have now been published online in the journal Nature Medicine in advance of their publication in the print edition.

Rare disease: Approx. 1,000 children affected

So far 1,000 children worldwide are affected by congenital disorders of glycosylation (CDG), which are classified as rare diseases. Affecting around 800 children, type CDG-Ia is most frequent. The number of unreported cases is high, however. Children with CDG are severely physically and mentally disabled, with approx. 20 percent dying before the age of two. To date, no therapy has been available to treat the disorder.

CDG-Ia is caused by mutations in the genetic information for the enzyme Phosphomannomutase 2 which is involved in important glycosylation processes: Mannose-1-phosphate is not produced in sufficient quantities. As a result, glycosylation malfunctions, meaning that sugar chains that normally aid in form, stability and function of the glycoproteins are not completely attached to the body's proteins or in some cases, are not attached at all. The lack of oligosaccharide chains leads to impairment of neurological, growth and organ development. The disorder only manifests if the baby inherits a mutated gene from both the mother and the father. The parents, who each carry one mutated and one "healthy" copy of the gene, do not exhibit any symptoms.

Mice take up mannose in drinking water

The mouse model developed by Prof. Körner and his team is characterized by mutations in the Phosphomannomutase 2 gene and demonstrates reduced enzyme activity, comparable to CDG-Ia in man. In their current study, the scientists exploited the ability of mannose to cross the placental barrier. This means that if the pregnant mouse takes up mannose, it also reaches the embryos in the uterus.

"One week prior to mating, we began giving the female mice mannose with their drinking water," explained biochemist Prof. Körner. The additional mannose supply up to birth increased the mannose levels in the embryos' blood. "The mice were born without defects and also after they were born, developed without any symptoms of the disorder, even if they no longer took up any mannose," Körner added. The successful studies performed by the Heidelberg University Hospital researchers clearly show the key role played by the supply of proteins with sugar chains during embryonic development.

New therapeutic approach

"Clinical studies in the U.S. and Germany have already been performed in which children with CDG-Ia were given mannose after they were born, either orally or by intravenous infusion. Unfortunately, these attempts have not been successful," explained Dr. Christian Thiel, head of the laboratory. "This means that the critical point at which it is possible to influence development must be during development in the uterus." For women with a risk of CDG-Ia, administering mannose during pregnancy may serve as a new therapeutic approach.

Shearing triggers odd behavior in microscopic particles

Microscopic spheres form strings in surprising alignments when suspended in a viscous fluid and sheared between two plates -- a finding that will affect the way scientists think about the properties of such wide-ranging substances as shampoo and futuristic computer chips. A team of scientists at Cornell University and the University of Chicago have imaged this behavior and have explained the forces causing it for the first time. Its findings appear in the Dec. 19-23 early edition of the Proceedings of the National Academy of Sciences.

"The experimental breakthrough revealed that these string structures were perpendicular to the shear instead of parallel to it, contrary to what many in the field were expecting," said Aaron Dinner, associate professor in chemistry at UChicago and a study co-author.

The experiment was led by Itai Cohen, associate professor of physics at Cornell, who custom-built a device that would enable him simultaneously to exert shearing forces on suspended colloids (the spheres) and image the resulting motion at 100 frames per second with a confocal microscope. Imaging speed was critical to the experiment because the string-like structures appear only at certain shear rates.

"This issue of strings has been pretty controversial. I'm not sure that we've solved all the controversies associated with them, but at least we've made a step forward," Cohen said.

Shearing forces affect the dynamic behavior of paint, shampoo and other viscous household products, but an understanding of these and related phenomena at the microscopic level has largely eluded a detailed scientific understanding until the last decade, Dinner noted.

Futuristically speaking, these forces potentially could be harnessed to produce microscopic patterns on computer chips or biosensors via special paints that flow easily when layered in one direction, but becomes hard when layered in another direction.

Cohen's objective was more scientifically immediate: to devise an experiment that would overcome the technical difficulties associated with measuring the mechanical properties of the colloidal strings while also imaging their formation. "The holy grail is to be able to understand how the structure leads to the mechanical properties and then to be able to control the mechanical properties by influencing the structure," Cohen explained.

Cohen, PhD'01, received his doctorate in physics at UChicago, as did lead author Xiang Cheng, PhD'09, a postdoctoral associate at Cornell who assembled the team; and co-author Xinliang Xu, PhD'07, a postdoctoral scholar at UChicago. The study co-authors also included Stuart Rice, the Frank P. Hixon Distinguished Service Professor Emeritus in Chemistry at UChicago and a 1999 recipient of the National Medal of Science.

As members of UChicago's Materials Research Science and Engineering Center, Rice and Dinner are part of a larger effort to determine how materials behave under the influence of various dynamic forces. Some of their physics colleagues analyze forces operating on macroscopic scales, while chemists such as Rice and Dinner attempt to assess how those findings might apply to microscopic phenomena.

Rice and his UChicago co-authors used computer simulations to develop a precise explanation for the string-like colloidal structures that formed in the Cornell experiment. "The previous simulations all left out the consequences of the flow created in the supporting fluid as the particles move, the so-called hydrodynamic forces," Rice said.

"A very large fraction of the work in the field neglects hydrodynamic forces because it's hard. You try and get away with what you can," Rice noted with amusement. "But in this case it turns out that the inclusion of those forces is the crucial element."

The simulations allowed the UChicago team to control various experimental parameters to assess their relative importance. "You can play God," Rice said. "The important finding is the overwhelming role of the lubrication forces and the anti-intuitive result that they create."

The lubrication force comes into play when two colloids come together to behave much like macroscopic ball bearings soaking in a reservoir of goopy fluid.

"Pulling them apart would be working against the fluid and so it would be very hard," Dinner said. "So actually, when you get a collision in these colloidal systems, those lubrication forces hold them together much longer, and that actually allows for some of the unique dynamics that give rise to the structure. That was specifically what the simulations showed."

Xu, the UChicago postdoctoral scholar, adapted a mathematical formula developed by John Brady at the California Institute of Technology to simplify the simulations, which ran for days and weeks at a time. "Every time you rearrange the particles, the interactions are different," Rice said. "If you were to calculate that directly, it would be extremely tedious."

But Xu's adapation of Brady's formula enabled him to generate a table of hydrodynamic interactions that listed each particle configuration. Xu found that he could accurately simplify the simulation by focusing on just two of the experiment's seven layers of colloids.

The simulations and the experiment showed that even after three centuries of study, the field of hydrodynamics continues to yield surprising discoveries. "We are still discovering novel behavior that is fundamentally determined by the hydrodynamics," Rice noted.

UTHealth researchers link multiple sclerosis to different area of brain

Radiology researchers at The University of Texas Health Science Center at Houston (UTHealth) have found evidence that multiple sclerosis affects an area of the brain that controls cognitive, sensory and motor functioning apart from the disabling damage caused by the disease's visible lesions. The thalamus of the brain was selected as the benchmark for the study conducted by faculty at the UTHealth Medical School. Lead researchers include Khader M. Hasan, Ph.D., associate professor, and Ponnada A. Narayana, Ph.D., professor and director of Magnetic Resonance Imaging (MRI) in the Department of Diagnostic and Interventional Imaging; and Jerry S. Wolinsky, M.D., the Bartels Family and Opal C. Rankin Professor in the Department of Neurology.

Results of the research were published in a recent edition of The Journal of Neuroscience.

"The thalamus is a central area that relates to the rest of the brain and acts as the 'post office,' " said Hasan, first author of the paper. "It also is an area that has the least amount of damage from lesions in the brain but we see volume loss, so it appears other brain damage related to the disease is also occurring."

Researchers have known that the thalamus loses volume in size with typical aging, which accelerates after age 70. The UTHealth multidisciplinary team's purpose was to assess if there was more volume loss in patients with multiple sclerosis, which could explain the dementia-related decline associated with the disease.

"Multiple sclerosis patients have cognitive deficits and the thalamus plays an important role in cognitive function. The lesions we can see but there is subclinical activity in multiple sclerosis where you can't see the changes," said senior author Narayana. "There are neurodegenerative changes even when the brain looks normal and we saw this damage early in the disease process."

For the study, researchers used precise imaging by the powerful 3 Tessla MRI scanner to compare the brains of 109 patients with the disease to 255 healthy subjects. The patients were recruited through the Multiple Sclerosis Research Group at UTHealth, directed by Wolinsky, and the healthy controls through the Department of Pediatrics' Children's Learning Institute.

Adjusting for age-related changes in the thalamus, the patients with multiple sclerosis had less thalamic volume than the controls. The amount of thalamic loss also appeared to be related to the severity of disability.

"This is looking at multiple sclerosis in a different way," Hasan said. "The thalami are losing cellular content and we can use this as a marker of what's going on. If we can find a way to detect the disease earlier in a more vulnerable population, we could begin treatment sooner."

The research was funded by a grant from the National Institutes of Health. The title of the article is "Multimodal Quantitative Magnetic Resonance Imaging of Thalamic Development and Aging Across the Human Lifespan: Implications to Neurodegeneration in Multiple Sclerosis."

Tuesday, 27 December 2011

Viagra against heart failure: Researchers at the RUB and from Rochester throw light on the mechanism

How sildenafil, the active ingredient in Viagra, can alleviate heart problems is reported by Bochum's researchers in cooperation with colleagues from the Mayo Clinic in Rochester (Minnesota) in the journal Circulation. They studied dogs with diastolic heart failure, a condition in which the heart chamber does not sufficiently fill with blood. The scientists showed that sildenafil makes stiffened cardiac walls more elastic again. The drug activates an enzyme that causes the giant protein titin in the myocardial cells to relax. "We have developed a therapy in an animal model that, for the first time, also raises hopes for the successful treatment of patients" says Prof. Dr. Wolfgang Linke of the RUB Institute of Physiology.

"Rubber band proteins" can be influenced

Sildenafil inhibits a specific enzyme (phosphodiesterase 5 A), which causes the increased formation of a messenger substance (cGMP). The messenger substance activates the enzyme protein kinase G, which attaches phosphate groups to certain proteins. This so-called phosphorylation causes blood vessels to relax, which was why the "potency pill" Viagra originally came onto the market. The Bochum and Rochester researchers found that the cardiac muscle protein titin is also phosphorylated through the same mechanism. "The titin molecules are similar to rubber bands" explains the Bochum physiologist. "They contribute decisively to the stiffness of the cardiac walls." The activity of the protein kinase G causes titin to relax. This makes the cardiac walls more elastic. The effect occurs within minutes of administering the drug.

Heart failure drugs currently not sufficient

"Of all the patients aged over 60 who are in hospital because of a weak heart, half suffer from diastolic heart failure" explains Linke. "Although we know that the decreased distensibility of the cardiac walls is the cause, the disease cannot be treated properly with today's medicines." In the so-called "Relax" study of the Heart Failure Network, the efficacy of sildenafil in people is already being tested. "If, for the first time, the drug is found to have a positive effect on heart failure, we would already have a molecular mechanism on hand to explain the effect" says Linke.

New suspect in 'Great Dying': Prehistoric blast

A great explosive burning of coal set fire and made molten by lava bubbling from the Earth's mantle , looking akin to Kuwait's giant oil fires but lasting anywhere from centuries to millennia, could have been the cause of  the world's most-devastating mass extinction, new research suggests.

The event, called the Great Dying, occurred 250 million years ago, at the end of the Permian period. "The Great Dying was the biggest of all the mass extinctions," said study researcher Darcy Ogden of the Scripps Institution of Oceanography in San Diego. "Estimates suggest up to 96 percent of all marine species and 70 percent of all land species were lost."

Researchers still debate the cause of this mass-extinction event, implicating everything from asteroids to volcanic eruptions to a decrease of the oxygen in the atmosphere.

Coal combustion
Studies earlier this year found evidence of a compound called fly ash, one of the products of coal combustion, in rocks laid down right before this extinction event. The finding suggested a large amount of coal had combusted over a period of tens to thousands of years.

The researchers already knew a series of volcanic eruptions, which gave rise to a region of volcanic rock called the Siberian Traps, occurred around this time and covered up to 2.7 million square miles in lava. These lava floods, made of molten basalt rock, could have taken out the animals and plants directly in their paths. To have any global impact, however, the volcanic eruptions also would have needed to send airborne ash, soot and gases high into the atmosphere, the researchers noted.

Coal also seems to have been present in the area of the Siberian Traps, and the researchers thought that perhaps the lava burned up a large amount of coal and left the fly ash — but they weren't sure whether it was physically possible. They ran computer simulations of these processes and found evidence that a coal explosion could have been the cause of worldwide climate change and the Great Dying.

Explosive extinction
These basalt floods could have mixed with the coal underground, then migrated up to the surface, where the mixture explosively lighted on fire when it mixed with oxygen in the air. [ Image Gallery: Wild Volcanoes ]

A blast that powerful "requires a very large amount of basalt to erupt over the surface in one place, and this place has to have large coal beds," Ogden said. "The Siberian Traps are a great candidate for this, since they are one of the biggest volcanic events in history and there is evidence to support the presence of coal in that region."

When this basalt-coal mixture reached the surface, it could have led to an explosive, fiery reaction similar to the giant oil fires set off by Iraqi forces in Kuwait in 1991. Volcanic emissions from the explosion would include carbon dioxide and methane, greenhouse gases that trap heat on Earth.

"The coal-basalt mixture comes out of the ground as a fluid, like oil, then ignites and combusts upon contact with the oxygen in the air," Odgen said. "The resulting soot, fly ash and gases are driven into the atmosphere in a large, dirty plume."

Pompeii column collapse revives concerns over site

A courtyard column of a Roman house in Pompeii collapsed on Thursday, renewing concerns about the state of the site which was frozen in time when Mount Vesuvius erupted 2,000 years ago, burying inhabitants alive and preserving their homes.

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Last year the Italian government was accused of neglecting the UNESCO World Heritage site near Naples in southern Italy when part of the "House of the Gladiators" fell down.

That collapse, along with three others in 2010, and the subsequent accusations of neglect and mismanagement, helped trigger a no-confidence vote against former culture minister Sandro Bondi in January.

Slideshow: World Heritage Sites (on this page)

Bondi, a member of former Prime Minister Silvio Berlusconi's centre-right government, survived the vote but quit in March.

Officials said the latest part of the site to crumble was one of several columns that once held up wooden trellises in the house where Loreio Tiburtino, a Roman nobleman, lived.

Built in the second century BC, the house was renovated in 62 AD, 17 years before the cataclysmic eruption.

"This is a torment without end," said Luisa Bossa, a lawmaker from the leftist opposition Democratic Party and former mayor of the Naples-area town of Herculaneum, also a major Roman-era archeological site.

"We have been complaining for three years but the country's most important archeological area continues to fall apart. The truth is that the site has been left alone for years and now, a bit at a time, we are paying the price," she said.

She called on Italy's culture minister, Lorenzo Ornaghi, to "take stock of the gravity of the situation and confront it with determination and speed."

Italy's archaeologists also voiced their concerns.

Slideshow: Italian dreams (on this page)

"To overcome the emergency created by these collapses, we need to hire specialized maintenance workers straight away. That is the only possible cure for Pompeii," Tsao Cevoli, head of the National Archaeologists Association, told news agency Ansa.

Pompeii was home to about 13,000 people when it was buried under ash, pumice pebbles and dust in 79 AD as it endured the force of an eruption equivalent to 40 atomic bombs.

Two-thirds of the 66-hectare (165-acre) town has since been uncovered. Pompeii attracts some 2.5 million tourists each year, making it one of Italy's most popular attractions.

Researchers: Video games won't make you smarter

Those action-packed video games under many Christmas trees on Sunday morning may be loads of fun, but don't expect them to improve kids' grades, concentration, driving skills or other cognitive abilities, one group of psychologists says.

Some researchers also say they've found video games such as current top-seller "Call of Duty: Modern Warfare 3" won't damage players' brains or cause them to do real violence.

Those relatively recent findings conflict with other studies on both the positive and negative potential of gaming, but one thing experts on all sides tend to agree about is that the debate — and their research — is far from over.

"Play these games because they are fun and you enjoy doing them, and let's kind of wait for more research to suggest whether or not they are actually good for us," said Florida State University psychologist Walter Boot.

Boot and two colleagues say they have turned up flaws in various studies ascribing cognitive benefits to playing video games and that they they've been unable to replicate the results. Boot, Florida State doctoral student Daniel Blakely and University of Illinois researcher Daniel Simons wrote about their findings in a paper published in the journal Frontiers in Psychology three months ago.

It "happens to be a rather direct attack about our work," University of Rochester researcher Daphne Bavelier wrote in an email Thursday from France where she is on sabbatical.

Bavelier defended studies she and other scientists have conducted that show a causal link between video game playing and enhanced abilities.

She said it is Boot and his colleagues who have flaws in their work and wrote a point-by-point rebuttal of their paper's detailed findings. It's also the only negative position paper aligned against multiple, peer-reviewed studies by "world renowned experts," she wrote.

"This paper does not present new evidence, or even new analysis — it is just an opinionated discussion of existing data," Bavelier wrote. "Quite simply put, there is not much controversy about the published effects so far."

Christopher Ferguson, a clinical psychologist at Texas A&M International University in Laredo, Texas, has focused on the perceived dark side of video gaming. As opposed to prior studies indicating violent games could beget violent actions, Ferguson said he found "nothing."

Studies on violence and video games have some of the same flaws Boot found for research on cognitive benefits, Ferguson said. He said that was probably because researchers drew conclusions before all the data was in.

"Video games had this sort of new toy effect," Ferguson said by phone from Orlando, where he was visiting relatives for the holidays. "People didn't know what to think about them and kind of got excited in both positive and negative ways."

This month's edition of the journal Nature Reviews/Neuroscience includes an article on video game research, describing it as being still in its early days. The journal posed several questions to prominent researchers and published their responses.

They include Bavelier, an assistant professor in Rochester's Department of Brain and Cognitive Science, and University of Minnesota psychologist C. Shawn Green, who submitted joint responses.

They maintained playing action video games "results in a wide range of behavioral benefits, including enhancements in low-level vision, visual attention, speed of processing and statistical inference."

Bavelier and Green also wrote there's no black-and-white answer to the question of whether video games improve cognitive function because there are millions of games and hundreds of genres that can be played on various devices including computers, consoles and cell phones.

"Simply put, if one wants to know what the effects of video games are, the devil is in the details," they wrote.

Two more scientists questioned by the journal also cited studies showing positive results two others wrote that effects on the brain and behavior are "uncertain" and that studies have not generally showing gaming enhances higher level reasoning.

Boot, 32, and Ferguson, 40, grew up playing video games. Ferguson said he still plays games such as "Lego's Star Wars" and "Indiana Jones" with his 8-year-old son. He suggested other parents do likewise.

"When they hear about 'Grand Theft Auto' or 'Medal of Honor' they get all freaky about it," Ferguson said.

But, he said, a colleague's research shows parents realize their fears were unjustified once they've played the games themselves.

Those trying to improve specific abilities such as driving a car or flying an airplane should look to simulators that focus on those skills instead of video games, Boot said.

"Simulate the demands that you'll actually encounter in those tasks rather than giving someone 'Grand Theft Auto' and assuming there's going to be some kind of magical transfer of skills that you pick up in that game to actual driving performance," he said.

There's also a proven alternative for boosting brain power that has other beneficial effects as well, Boot said. It's called exercise.

"Don't sit down and play a game," he said. "Go out there for a walk."

Rudolph's red nose has nothing on his eyes

The reindeer of Christmas myth must meet high expectations this time of year — not just hauling heavy loads of gifts over long distances — but also helping navigate from the tundra to the rest of the world.

And even though most real reindeer never pull sleighs through snowy nights, new research suggests that their eyes would be far better suited to the task than Santa's are. Unlike people, the study found, reindeer can see ultraviolet light — which probably allows them to detect food and predators in a mostly white environment.

The study makes reindeer the first large mammal known to have UV vision. And it raises questions about how animals that are highly specialized to their environments will adapt as their environments change.

"Reindeer are mammals and what we find may be related to humans," said Karl-Arne Stokkan, an Arctic biologist at the University of Tromsø in Norway. "In the view of potential climate change, we have also realized that reindeer may be an important 'signal-animal' because of their strong adaptation to an environment believed to suffer the biggest changes."

Many animals are able to see or respond to ultraviolet light, including some birds, rodents, fish, bees and bats. But UV light is invisible to the human eye and with enough exposure, can even cause damage. Most dangerous are bright, snowy and icy conditions at high elevations or high latitudes, where lots of UV intensity and reflectivity can cause snow blindness in human eyes.

Since reindeer live in the Arctic, where levels of ultraviolet light are at their highest in proportion to other wavelengths, Stokkan and colleagues wondered if the animals might have evolved a way to deal with a world full of ultraviolet radiation. In a lab experiment with LED lights, the researchers first showed that UV light passed right through the reindeer's cornea and lens into its retina, they reported in the Journal of Experimental Biology.

In human eyes, the lens instead acts as a UV filter, said Marty Banks, a vision scientist at the University of California, Berkeley. That prevents ultraviolet light from reaching the retina, where it can cause damage.

Next, the researchers used anesthetized reindeer to demonstrate that cells in the retina responded electrically to UV signals. Similar tests on other kinds of deer have previously come up negative, Stokkan said.

Ultraviolet vision may be a specialized adaptation to life in the snowy Arctic, the researchers hypothesize. Reindeer eat lichen, which absorb UV light, and they try to avoid being eaten by wolves, whose fur also absorbs the UV spectrum. Being able to see ultraviolet wavelengths, then, may give the animals the ability to see contrasts, helping them find food and avoid predators when surrounded by reflective snow and ice.

UV vision might also help reindeer distinguish subtle contours in what might look like a flat landscape of snow, which would help them navigate safely.

The animal kingdom contains a wide variety of designs for eyes and visual systems that can be wildly different form how humans see, Banks said. But research on animal eyes often helps scientists better understand the ways that vision works in people.

Work on chickens, for example, has led to a theory that the growing use of computers, books and cell phones might explain a rapid rise in nearsightedness over the past 60 years or so. Researchers have also recently discovered a new kind of ultraviolet light-sensing receptor in many animals that seems to play a role in regulating circadian rhythms.

Figuring out how reindeer manage to let ultraviolet rays into their eyes without going blind might end up having applications for mountaineers and others.

"How does a reindeer get away with it and not have the health consequences that we have if we're exposed to a lot of UV light?" Banks said. "For humans, the sum total of UV light exposure over a lifetime is predictive of a lot of bad things that we don't want to have. That might help us understand how to protect people more."

Scientific reasons for Earth’s seasons

The seasons are a powerful force in our lives. They affect the activities we do, the foods we crave, the clothes we wear — and quite often, the moods we are in. The seasons officially change once again on Thursday, with winter beginning in the Northern Hemisphere and summer starting in the south.

What is it that causes the change in seasons?

The ability to predict the seasons — by tracking the rising and setting points of the sun throughout the year — was key to survival in ancient times. The Babylonians, the Maya and other cultures developed complex systems for monitoring seasonal shifts. But it took centuries more to unravel the science behind the seasons.

Nicolai Copernicus (1473-1543) radically changed our understanding of astronomy when he proposed that the sun, not Earth, was the center of the solar system. This led to our modern understanding of the relationship between the sun and Earth.

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We now know that Earth orbits the sun elliptically and, at the same time, spins on an axis that is tilted relative to its plane of orbit. This means that different hemispheres are exposed to different amounts of sunlight throughout the year. Because the sun is our source of light, energy and heat, the changing intensity and concentration of its rays give rise to the seasons of winter, spring, summer and fall.

Solstices and equinoxes
The seasons are marked by solstices and equinoxes — astronomical terms that relate to Earth’s tilt.

The solstices mark the points at which the poles are tilted at their maximum toward or away from the sun. This is when the difference between the daylight hours and the nighttime hours is most acute. The solstices occur each year on June 20 or 21 and Dec. 21 or 22, and represent the official start of the summer and winter seasons.

The vernal equinox and autumnal equinox herald the beginning of spring and fall, respectively. At these times of the year, the sun appears to be directly over Earth’s equator, and the lengths of the day and the night are equal over most of the planet.

On March 20 or 21 of each year, the Northern Hemisphere reaches the vernal equinox and enjoys the signs of spring. At the same time, the winds turn colder in the Southern Hemisphere as the autumnal equinox sets in.

The year's other equinox occurs on Sept. 22 or 23, when summer fades to fall in the north, and winter’s chill starts giving way to spring in the south.

From year to year, there is always some variability in the equinoxes and solstices because of the way Earth's changing tilt matches up with its orbit around the sun. This year, the precise moment of the December solstice comes at 12:30 a.m. ET Thursday. That's the moment when Earth's north pole is tipped to the maximum amount in the sun's direction.

Thursday thus represents the longest night of the year for the Northern Hemisphere's residents, and the longest duration of daytime south of the equator.

Effect on climate
Here’s how the seasonal change affects the weather: Around the time of the June solstice, the North Pole is tilted toward the sun and the Northern Hemisphere is starting to enjoy summer. The density of the solar radiation is higher because it's coming from directly overhead — in other words, the sun's rays are concentrated over a smaller surface area. The days are longer, too, meaning that more radiation is absorbed in northern climes during the 24-hour cycle. Another factor that may come into play is that the radiation takes a somewhat shorter path through the energy-absorbing atmosphere before striking the earth.

At the same time that the Northern Hemisphere is entering summer, the South Pole is tilted away from the sun, and the Southern Hemisphere is starting to feel the cold of winter. The sun’s glancing rays are spread over a greater surface area and must travel through more of the atmosphere before reaching the earth. There are also fewer hours of daylight in a 24-hour period.

The situations are reversed in December, when it’s the Southern Hemisphere that basks in the most direct rays of the sun, while the Northern Hemisphere receives less dense solar radiation for shorter periods of time.

Although the solstices represent the pinnacles of summer and winter with respect to the intensity of the sun’s rays, they do not usually represent the year's warmest or coldest days. This is because temperature depends not only on the amount of heat the atmosphere receives from the sun, but also on the amount of heat it loses due to the absorption of this heat by the ground and ocean.

It is not until the ground and oceans absorb enough heat to reach equilibrium with the temperature of the atmosphere that we feel the coldest days of winter or hottest days of summer.

Monday, 26 December 2011

Spiders' sexual cannibalism is for offspring

The unkind act of butchering and eating your mate after sex, typified by the female black-widow spider and praying mantis, may make for healthier babies, new research suggests.

The researchers found that a male orb-web spider makes the ultimate evolutionary sacrifice: giving his life for the health of his offspring.

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Sexual cannibalism is the act of one partner eating the other after sex. In the orb-web spider Argiope bruennichi, the female tries to grab and wrap up the male at the onset of mating so she can snack on him during sex. In the lab, only about 30 percent of the males survive their first mating, but by letting the female gnaw on them, the males prolong the sex act, making it more likely they will inseminate their partner.

Of these survivors, half go on to find a second mate, while the others try again for the same female. Due to the male's anatomy, two copulations is the limit. (When you are facing a life without sex, is it really worth it to go on?)

"Two main hypotheses explain the evolution of sexual cannibalism," study researcher Klaas Welke, of the University of Hamburg in Germany, told LiveScience in an email. The males might be offering themselves up "to gain access to mating opportunities and to prolong their mating duration." Or, Welke said, it could be a "paternal investment into their own offspring, and they provide females with nutrients."

In the case of the orb-web spider, males tend to be much smaller than their mates ; in this species, they're only one-tenth as heavy, and researchers weren't sure how much nutritional benefit the females can gain from such pipsqueak partners.

To see if eating their mates gave female spiders a nutritional advantage, the researchers divided the female orb-web spiders of their laboratory collection into three groups, allowing them to mate with one, two or three males. Half of each group of females also was allowed to eat their mates, while in the other instances, the researchers reached in and saved the male from his partner's clutches.

They then analyzed each female's eggs and resulting offspring. They counted and weighed the eggs and monitored how many offspring survived simulated cold-weather scenarios — about 46 degrees Fahrenheit (8 degrees Celsius) — and a 20-week stint of starvation.

The researchers thought that perhaps the nutritional bonus from multiple mates and meals would have an impact on females. It didn't. "We were surprised, because we had expected that any effect of male consumption would increase with every additional male consumed," Welke said.

What they did see, however, was that any cannibalism led to healthier offspring that survived better and had bigger eggs.

"Our findings suggest a paternal investment of males into their offspring," Welke said. "Sexual cannibalism may increase male reproductive success and may be very beneficial in a species with a high paternity insurance and a low rate of polyandry as found in Argiope bruennichi."

Track Santa on your smartphone

the North American Aerospace Defense Command — has used its high-tech missile-tracking systems to track Santa's progress during his annual Christmas Eve flight around the world.

For a 24-hour period, about 1,200 military volunteers take shifts manning the command center at Peterson Air Force Base in Colorado; they monitor radar screens and field calls from excited 7-year-olds who ask for updates on Santa's location. They also update Kris Kringle's progress on the Google Earth map on the NORAD Tracks Santa website, as well as the Facebook page and the Twitter feed.

For the first time this year, people can even keep constant tabs on Santa's sleigh by downloading the NORAD Tracks Santa iPhone and Android apps. In other words, the program is a big deal, and it get bigger every Christmas.

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But how do they do it? How does NORAD "track" Santa? [ Is There a Santa Claus? ]

When asked whether the volunteers plan the jolly old elf's route ahead of time, U.S. Navy Lieutenant Commander Bill Lewis, a Santa tracker, was having none of that.

"We don't plan it, he does," Lewis said. "We just monitor his travels with our ground-based radar, satellites, fighter aircraft, and, of course, the Santa Cams — he passes over certain cities, and based on the track we're projecting, we've got cameras set up."

The NORAD team monitors a radar system called the North Warning System, which consists of 47 installations strung across the northern border of North America, for indications that Santa Claus has left the North Pole.

"Rudolph's nose puts off quite the heat signature," Lewis told Life's Little Mysteries.

The Christmas program isn't so out of the ordinary for the men and women of NORAD: "365 days a year we track possible threats to the homeland. So tracking Santa as an airborne object fits into our mission set," he said.

Through his experience as a Santa Tracker, Lewis was able to offer a bit of insight into an age-old question: How Santa manages to make it all the way around the world, sort through Can Tech Help Santa Deliver the Goods? 5 Tech Upgrades for Claus ]

That's 671 million miles (1 billion kilometers) per hour, which means Santa can travel more than 16 billion miles (26 billion km) in the 24 hours allotted for his journey. A trip round the world is only 25,000 miles (40,000 kilometers), so at his estimated flight speed, Santa could technically circumnavigate Earth 650,000 times if he wanted.

He doesn't, of course — instead, he takes it slow and downs a mindblowing number of cookies and glasses of milk along the way.

Was Shroud created in a flash? Claims rise again

The Shroud of Turin bears the faded image of what appears to be a Christlike figure. Italian researchers say they've come close to the shroud's coloration by blasting strips of linen with ultraviolet laser light.

Italian researchers have resurrected the idea that the Shroud of Turin's mysterious image of a Christlike figure could only have been created by a powerful flash of light — but skeptics still aren't buying it.

Scientists have tussled with believers, and with each other, over the origins of the centuries-old cloth for decades: Many believers think it's the true image of Jesus, left behind miraculously on his burial cloths after his resurrection. Analyses of the Shroud's chemical makeup, as well as radiocarbon dating of fiber samples, have led lots of researchers to conclude that the image was painted onto the cloth during the 14th century. But other researchers, sympathetic to the Shroud's cause, say those tests were faulty.

The Italian studies, conducted at the ENEA Research Center in Frascati, addresses a specific question in Shroud science: Could a burst of radiation have created the coloration seen on the linen? The answer is yes, although the results reported in the latest studies aren't a perfect match. So does that mean the Shroud image could only have been created by the flash of a miraculous resurrection? The answer is no, despite what you might read on the Web.

Five years of tests
"Sadly, we have seen many claims spread in the Web made by journalist/bloggers that discuss the content of a paper they never read," lead researcher Paolo Di Lazzaro told me today in an email. "It is obvious that a serious scientific work cannot prove any supernatural action. We have shown that the most advanced technology available today is unable to replicate all the characteristics of the Shroud image. As a consequence, we may argue it appears unlikely a forger may have done this image with technologies available in the Middle Ages or earlier. The probability the Shroud is a medieval fake is really low. In this sense, the Shroud image is still a scientific challenge."

Di Lazzaro and his colleagues based their conclusions on five years of tests, using an ultraviolet laser apparatus and strips of modern-day linen. They blasted the cloth with UV at different power levels, and reported that they "achieved a very superficial Shroud-like coloration of linen yarns in a narrow range of irradiation parameters." The best effect depended on laser pulses lasting less than 50 nanoseconds.

"These processes may have played a role in the generation of the body image on the Shroud of Turin," the researchers report.

They don't go so far as to claim a miracle. But the fact that UV laser blasters didn't exist in the 13th century, let alone in Jesus' day, strongly implies that they suspect something out of the ordinary was going on.

What do you think of the Shroud of Turin?

Di Lazzaro told me that the tests were not financed by ENEA, which is a government-sponsored research agency, and were conducted outside working hours. "The research was curiosity-driven, the attempt to replicate an image which is considered 'the impossible image' due to its very peculiar characteristics," he said.

Over the years, Di Lazzaro and his colleagues have published a long list of studies, including peer-reviewed papers (see below). The latest studies were presented at a May conference in Frascati and published in November as an ENEA technical report (with a disclaimer saying that the contents didn't necessarily express ENEA's opinion). But they didn't really get traction until this week, just in time for Christmas, thanks to a series of sensationalized British news reports.

Critiquing Shroud science
Shroud science, also known as sindology, usually percolates outside the scientific mainstream — but every once in a while a sensational claim comes into the public spotlight. Joe Nickell, an investigator for the New York-based Center for Inquiry, has been following sindology for decades. He noted that the Italian research revives a discussion going back to the 1980s, spearheaded by a group called the Shroud of Turin Research Project, or STURP.

"This is really nothing new," Nickell told me today. "This is a supposed vindication of STURP."

Nickell said Di Lazzaro and his colleagues started out with the assumption that the coloration on the Shroud couldn't have been created by applying pigment to the linen — which runs counter to the conclusions drawn by other studies. Starting out with the idea that the human figure shown on the Shroud is an "impossible image" stacks the deck in favor of a miraculous explanation, he said.

"Making the assumption of a miracle is a really, really, really, really, really big assumption," Nickell said. "That it's done in the name of science is just astonishing."

Nickell said the latest findings don't prove much of anything, even though they're dressed up in high-tech tests.

"It is made up of whole cloth," he said. "The pro-Shroud people start with the answer, and then they have to get some scientific evidence to back this up."

Weird wildlife: Real animals of Antarctica

Ask anyone to name an Antarctic land animal, and chances are the response will be, "penguin." Try again, says David Barnes, a scientist with the British Antarctic Survey.

"Penguins aren't really residents on land. All the species except for one — emperor penguins — spend most of their lives at sea," Barnes told OurAmazingPlanet.

"And likewise the other sea birds go north during Antarctica's winter," he added.

It turns out that the usual suspects — penguins, seals — don't actually live on the continent. They just visit.

"In order to see Antarctica's resident land animals, you have to have a microscope," Barnes said.

And one look reveals an outlandish cast of characters more suited to Lewis Carroll's fiction than a Disney movie, both in name and ability. The continent's natives — rotifers, tardigrades and springtails, collembola and mites — possess a bizarre array of physiological tools to survive on the coldest, windiest, highest and driest continent on Earth.

In addition, evidence is mounting that these weird Antarctic animals are remnants of a bygone age, the only survivors of a vanished world — something once thought nearly impossible.

"The take-home message is that we think our animals survived the last ice age," said biologist Byron Adams, a professor at Brigham Young University.

Petite pachyderms
The largest of the continent's land animals, the so-called "elephants of Antarctica," are the collembola, or, as they are more commonly known, springtails. Unlike the majority of their neighbors, they are visible to the naked eye.

"They look like insects — a little bit like an earwig," said Ian Hogg, a freshwater ecologist and associate professor at New Zealand's University of Waikato. "But they're a lot cuter than earwigs," Hogg added.

Typically under a millimeter long, the tiny, six-legged arthropods are similar to insects, but more primitive, and likely resemble the ancient ancestors of modern-day insects,  Hogg said. They live under rocks near coastal areas, and survive on a diet of fungus and bacteria. Hogg has found them as far south as 86 degrees latitude.

Although springtails are found all over the planet, those that live in Antarctica have a few tricks to survive the brutal conditions. They can slow down their metabolism to save energy, "and when it gets close to winter, they start to produce glycerol, which lowers their freezing point," Hogg said.

But even springtails can succumb in harsh Antarctic conditions. "If they get too cold they'll freeze solid, and that's the end of them," Hogg said.

They're aliiiive
Yet for Antarctica's most abundant land animal, tiny nematode worms, freezing is not fatal — it's more like a neat party trick.

The hardy worms are one of the most abundant creatures on Earth, and in Antarctica's simple ecosystems, they are king.

"They're the rulers of the continent," said BYU's Byron Adams. "As far as animals go, you're more likely to find a nematode than anything."

The worms may be tiny — a real whopper is almost as long as a dime is thick, Adams said — but they have the combined biological powers of a MacGyver and a Lazarus.

First, the worms employ inventive physiological processes to stave off the effects of the extreme cold.

Like springtails, Antarctica's nematodes can lower their freezing point. They also have a mechanism to protect their cells from the dangers of frozen water, allowing them to survive in temperatures well below freezing.

Inside a cell, ice can be deadly. "Imagine a drop of water," Adams said. "It's smooth and round. When that turns into ice, it turns into a ninja-star type of thing, with all these sharp points. That causes the cells to burst — it kills the cell," he said. This same process causes frostbite and its nasty effects. As cells die, tissue is destroyed.

To prevent this, nematodes produce proteins that act as packing peanuts, surrounding the sharp-edged ice crystals with tiny cushions to protect the cells from rupture and ensuing death.

When conditions get too dry (the worms require moisture to function), the worms have the ability to drop into a death-like state of suspended animation from which they can revive many months, even decades, later, when conditions improve.

"They pump all the water out of the bodies until they're dried out like a little Cheerio," Adams said — a process similar to freeze-drying. The worms then literally just blow around in the wind until water returns — often, not until the following summer, when melt from glaciers creates freshwater streams around the continent.

"When the water comes back, the nematodes suck the water back into their bodies and they're re-animated — they come back to life," Adams said.

The strategy is not unique to Antarctica. Nematodes that live in hot, dry deserts do the same thing, he added.

It's still not clear just how long the worms can survive in this state, but nematodes have reawakened after 60 years in freeze-dried mode.

For all their toughness, the nematodes may have reason to envy one of their Antarctic colleagues — tardigrades — which are similarly rugged, yet have one thing nematodes just haven't got: good looks.

Brawny beauties
"They're really cute," Adams said.

Tardigrades look a bit like a bear crossed with a sweet potato. In fact, they look huggable — a rare quality among microscopic animals. They have chubby bodies and eight legs, from which curved, bear-like claws protrude.

Like nematodes, these algae-eating water beasts can "freeze-dry" themselves, and have even survived a trip into low-Earth orbit.

"It was quite surprising to me that exposure to the vacuum of space, with its extreme desiccating effect, did not affect survival at all," said Ingemar Jönsson, a professor at Sweden's Kristianstad University, in an email. Jönsson orchestrated the tardigrade space trip aboard a European Space Agency craft in 2007.

Where'd you come from?
The two remaining major Antarctic residents are mites — tiny arachnids that live alongside springtails under rocks — and rotifers, microscopic, slinky-like creatures that dwell alongside nematodes and tardigrades in more moist environments. Although there are many species of each, it's astonishing to essentially be able to count the land animals of an entire continent on one hand.

And although these extreme organisms use a range of biological stunts to survive in Antarctica, they can't live in the ice itself, and it was long accepted that the animals were fairly new arrivals.

"The dogma is that in the last glacial, the continent was totally covered with ice and there was no life," Adams said. "That would mean that all the organisms that live there had to have moved back there since the last glacial maximum — in the last 12 (thousand) to 20 thousand years." That's when retreating ice would have exposed bits of land fit for habitation.

"The problem with that is almost all the animals we find in Antarctica are indigenous to Antarctica," he said. "They're not found anywhere else in the world, and they're not closely related."

Genetic evidence suggests that the continent's residents must have stuck it out through the last glacial maximum. That, in essence, they've been there since 100,000 years ago, when the planet began to cool.

This, along with geological evidence, is changing some of the accepted thinking. Now many Antarctic scientists think the continent wasn't entirely icebound during the last glacial maximum. "We think that there were areas that were exposed, and that these animals survived in little pockets — and once the ice sheets receded, they expanded their range."

Essentially, the crushing cold and lack of moisture killed off the continent's more delicate beasts, and left behind only the hardiest. With almost no competitors for the limited resources, Antarctica's tiny animals were suddenly the smartest guys in the room, able to move out and take over the continent.

Tense future
Even as researchers are learning more about the past of Antarctic wildlife, they are using the continent's residents to peer into the future.

"What is really fascinating about working in Antarctica, is that we can look at the effect of climate change on a single species in the soil," said Diana Wall, a soil ecologist at Colorado State University who has studied Antarctica's tiny animal life for more than two decades.

"We can't do that with a single species anywhere else — the communities are so complex," she said.

Hogg agreed. "Antarctica is such a simple system. The springtails are the biggest things you have to worry about," he said. "And the changes down there happen much more quickly than they will in more temperate latitudes, so it makes it a really fascinating place to look at these changes and how things might respond."

The continent serves as a pristine, natural laboratory, Adams said.

"If you take a sample from a beach in Florida, and you get an anomalous reading, it could be due to anything" he said. "Where we're working in Antarctica, we don't have any of those variables."

Ironically, because Antarctica has no native human population (along with the inevitable environmental footprints we leave behind), it's one of the best places on Earth to study how changing climate will affect the places people do live, Adams said.

"Someone might say, 'Well, springtails aren't very exciting animals,'" Hogg said. However, he added, studying them and their Antarctic neighbors, which all play a role in cycling nutrients through the environment, can help illuminate how ecosystems closer to home might change with the climate.

More science news from MSNBC Tech & Science Was Shroud created in a flash? Claims rise again Science editor Alan Boyle's blog: Italian researchers resurrect the idea that the Shroud of Turin's mysterious image could only have been created by a powerful flash — but skeptics still aren't buying it.

Who's afraid of a 13-foot-tall walking robot? Ancient green grocer target of fiery curse You do the math — because that pigeon can

"It can help us learn about agricultural systems and the places that we care about and rely on for our daily well-being," he said

"It's very appealing to those of us who are trying to get to the bottom of the fundamentals of the relationship between biodiversity and climate change," Adams said. "This is the one place where we can do these experiments in a natural system."

You do the math — because that pigeon can

Pigeons may not be so bird-brained after all, as scientists have found the birds' ability to understand numbers is on par with that of primates.

Previous studies have shown that various animals, from honeybees to chimpanzees, can learn to count when trained with food rewards. In 1998, researchers discovered that rhesus monkeys can not only learn to count to four, but can also pick up on numerical rules and apply them to numbers they haven't seen before, allowing them to count up to nine without further training.

With this finding in mind, psychologists at the University of Otago, in New Zealand, sought to find out if pigeons — another animal shown to count — have a numerical competence similar to rhesus monkeys.

" Pigeons are the perfect subjects for visual tasks, because their vision is really good and they're really easy to train," said psychologist Damian Scarf, first author of the new study. "It appears that you can train them on almost any task you can train monkeys on."

Scarf and his colleagues first trained three pigeons to count up to three. On a touchscreen, they presented the pigeons with a set of images that had objects of various sizes, shapes and colors. For example, one set presented images with one yellow block, two red cylinders or three yellow rectangles. To receive a treat, the pigeons had to select the images in the correct object-number order, from lowest to highest.

Once the birds learned to count to three, the researchers began showing the pigeons images with up to nine objects. On average, without higher-number training or food rewards, the pigeons were able to correctly order the image sets over 70 percent of the time. The pigeons had an easier time discriminating between lower numbers and numbers that were further apart.

"Once you start getting up towards seven, eight and nine, it was very difficult for (the pigeons) to tell the difference between the images," Scarf told LiveScience. Overall, the results of the study echoed those of the rhesus monkey research, though Scarf noted it took longer to train the pigeons than other researchers took training monkeys.

William Roberts, a University of Western Ontario psychologist who was not involved in the research, was surprised by the study's results. "I didn't anticipate that pigeons could have done that," said Roberts, who has previously researched animal cognition, including pigeon intelligence.

Roberts is curious to see how widespread this ability is in the animal kingdom. "Can we find evidence for this type of counting in insects, particularly bees?" he said. Finding the same level of numerical competence as the pigeons (and rhesus monkeys) in other species would help scientists understand if the ability evolved across species separately, or if a common ancestor shared the ability.

"We now have another piece of (the) puzzle," said Scarf, who is interested in performing similar experiments in parrots and other intelligent birds. "What's the origin of the ability?"

Saturday, 24 December 2011

2011 Nobel Laureate Ralph Steinman Explains Discovery of Cells Used for Cancer Treatment [Video]

In the quest to cure cancer, many researchers have started looking beyond toxic chemicals and harsh radiation and instead are trying to harness the body's immune system.

Ralph Steinman made a landmark discovery about the immune system in the 1970s when he first described dendritic cells with the help of his mentor Zanvil Cohn at Rockefeller University. More than 30 years later, when Steinman was diagnosed with pancreatic cancer, these cells served as the basis of his experimental treatments.

He won the 2011 Nobel Prize for Medicine or Physiology for his early-career discovery but died just three days before the official announcement. In the January 2012 issue (to be released online December 20, 2011), Scientific American chronicles Steinman's early find and how the cells became an integral part of his unconventional battle with pancreatic cancer.

In the following video, filmed when he won the 2007 Albert Lasker Award for Basic Medical Research, Steinman recounts his discovery of biology—and of the amazing cells that likely helped to keep him alive years longer than expected.

For more videos of Steinman discussing dendritic cells and their role in the immune system, visit the collection of his interviews on the Lasker Foundation's website.

2-Degree Global Warming Limit Is Called a "Prescription for Disaster"

A mantra that has driven global negotiations on carbon dioxide emissions for years has been that policy-makers must prevent warming of more than two degrees Celsius to prevent apocalyptic climate outcomes. And, two degrees has been a point of no return, a limit directly or indirectly agreed to by negotiators at international climate talks.

James Hansen, director of the NASA Goddard Institute for Space Studies in New York, whose data since the 1980s has been central to setting that benchmark, said today that two degrees is too much.

New, extensive study of the paleoclimate record going back 50 million years by Hansen and others now shows that the two-degree target for global temperature rise “is a prescription for disaster,” Hansen said here at a news conference during the American Geophysical Union meeting.

Hansen came to that conclusion after reviewing average and extreme perturbations in the paleoclimate record that have been more thoroughly documented in the past few years. The record shows that 50 million years ago, Earth was free of ice, and sea level was 70 meters higher on average than it is today. Both phenomena resulted from natural variations in mean temperatures due to slight changes in the sun’s output and Earth’s orbit over geological time scales. Rising temperatures today, over far shorter time scales in which neither the sun nor the orbit are factors, are caused primarily by higher levels of CO2 and other greenhouse gases in the atmosphere.

Atmospheric carbon dioxide levels before the industrial revolution were about 280 parts per million on average. They have been rising ever since, and today are about 397 ppm. A level of 450 ppm has generally been associated with an average global temperature rise of two degrees C. However, the latest analysis shows that a level of 450 ppm is enough to melt a significant portion of the world’s ice, because feedback mechanisms kick in; melting ice hastens the melting of even more ice, for example, and thawing permafrost emits methane that accelerates warming, prompting permafrost to thaw even more.

If the number reaches 560 ppm, a doubling of preindustrial values, sea level globally could rise 25 meters, according to Eelco Rohling, professor of ocean and climate change at University of Southampton in the U.K., who presented data at the AGU meeting with Hansen. Many large cities worldwide lie at that elevation or lower. The two scientists agreed that if nations continue to emit CO2 at current rates, the world could reach 560 ppm by 2100.

The paleoclimate record also shows that 560 ppm would be enough to melt all the ice in the Arctic, and later the Antarctic. Rohling said that once the Antarctic melts, sea levels would rise by 60 to 70 meters. “If governments keep going the way they are going,” Hansen added, “the planet will reach an ice-free state.”

Hansen concluded with a message to negotiators at the current climate talks in Durban, South Africa. If the world begins reducing CO2 emissions by 6 percent a year starting in 2012, Hansen said, atmospheric levels can return to the “safe” level of 350 ppm that he and others have long called for. “If the world waits until 2020 to begin,” he noted, “it will need to reduce CO2 by 15 percent a year to reach 350 ppm. We are out of time.”

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