Computer chips of a type more commonly found in games consoles have been used by scientists at the University of Bristol to reveal how the flu virus resists anti-flu drugs such as Relenza and Tamiflu.
Professor Adrian Mulholland and Dr Christopher Woods from Bristol's School of Chemistry, together with colleagues in Thailand, used graphics processing units (GPUs) to simulate the molecular processes that take place when these drugs are used to treat the H1N1-2009 strain of influenza -- commonly known as 'swine flu'.
Their results, published May 29 in Biochemistry, provide new insight that could lead to the development of the next generation of antiviral treatments for flu.
H1N1-2009 is a new, highly adaptive virus derived from different gene segments of swine, avian, and human influenza. Within a few months of its appearance in early 2009, the H1N1-2009 strain caused the first flu pandemic of the 21st-century.
The antiviral drugs Relenza and Tamiflu, which target the neuraminidase (NA) enzyme, successfully treated the infection but widespread use of these drugs has led to a series of mutations in NA that reduce the drugs' effectiveness.
Clinical studies indicate that the double mutant of swine flu NA known as IRHY2 reduced the effectiveness of Relenza by 21 times and Tamiflu by 12,374 times -- that is, to the point where it has become an ineffective treatment.
To understand why the effectiveness of Relenza and Tamiflu is so seriously reduced by the occurrence of this mutation, the researchers performed long-timescale molecular dynamics (MD) simulations using GPUs.
Professor Mulholland said: "Our simulations showed that IRHY became resistant to Tamiflu due to the loss of key hydrogen bonds between the drug and residues in a part of the NA's structure known as the '150-loop'.
"This allowed NA to change from a closed to an open conformation. Tamiflu binds weakly with the open conformation due to poor electrostatic interactions between the drug and the active site, thus rendering the drug ineffective."
These findings suggest that drug resistance could be overcome by increasing hydrogen bond interactions between NA inhibitors and residues in the 150-loop, with the aim of maintaining the closed conformation.
Read more at Science Daily
May 29, 2012
16th-Century Korean Mummy Provides Clue to Hepatitis B Virus Genetic Code
Additional analysis of the ancient HBV genomes may be used as a model to study the evolution of chronic hepatitis B and help understand the spread of the virus, possibly from Africa to East-Asia. It also may shed further light on the migratory pathway of hepatitis B in the Far East from China and Japan to Korea as well as to other regions in Asia and Australia where it is a major cause of cirrhosis and liver cancer.
The reconstruction of the ancient hepatitis B virus genetic code is the oldest full viral genome described in the scientific literature to date. It was reported in the May 21 edition of the scientific journal Hepathology by a research team from the Hebrew University of Jerusalem's Koret School of Veterinary Medicine, the Robert H. Smith Faculty of Agriculture, Food and Environment; the Hebrew University's Faculty of Medicine, the Hadassah Medical Center's Liver Unit; Dankook University and Seoul National University in South Korea.
Carbon 14 tests of the clothing of the mummy suggests that the boy lived around the 16th century during the Korean Joseon Dynasty. The viral DNA sequences recovered from the liver biopsy enabled the scientists to map the entire ancient hepatitis B viral genome.
Using modern-day molecular genetic techniques, the researchers compared the ancient DNA sequences with contemporary viral genomes disclosing distinct differences. The changes in the genetic code are believed to result from spontaneous mutations and possibly environmental pressures during the virus evolutionary process. Based on the observed mutations rates over time, the analysis suggests that the reconstructed mummy's hepatitis B virus DNA had its origin between 3,000 to 100,000 years ago.
The hepatitis B virus is transmitted through the contact with infected body fluids , i.e. from carrier mothers to their babies, through sexual contact and intravenous drug abuse. According to the World Health Organization, there are over 400 million carriers of the virus worldwide, predominantly in Africa, China and South Korea, where up to 15 percent of the population are cariers of the virus. In recent years, universal immunization of newborns against hepatitis B in Israel and in South Korea has lead to a massive decline in the incidence of infection.
Read more at Science Daily
Occupy the Neolithic: Social Immobility in the Stone Age
Most researchers agree that social hierarchies began with the advent of farming. The earliest known farming communities are found in the Near East, dating back almost 11,000 years. Archaeologists have looked for evidence of social stratification in these societies with mixed results. Some early farming societies show signs that people played different roles and that some were buried with greater ritual — shuffling off this mortal coil with a number of elaborate “grave goods,” including pottery and stone tools. However, there is little evidence that social inequality was hereditary or rigidly defined.
That seems to have changed sometime after farmers moved into Europe from the Near East, beginning about 8,500 years ago during a period known as the European Neolithic. One of the best studied farming cultures is the Linearbandkeramik (LBK), which arose in what is today Hungary about 7,500 years ago and spread as far as modern-day Paris within 500 years, after which it appears to have been superseded by other cultures.
Archaeologists have long noted signs that the LBK culture might have been socially stratified. For example, some, but not all, males were buried with stone tools called adzes, which were thought to be used to build the wooden houses in which the farmers lived. But a few researchers have argued that this stratification took place only gradually over the 500-year period of the LBK.
To get a better handle on the timing and nature of these social inequalities, a team led by Alexander Bentley, an archaeologist at the University of Bristol in the United Kingdom, analyzed the tooth enamel from more than 300 skeletons from seven LBK burial sites across Europe. These cemeteries, located in the Czech Republic, Slovakia, Austria, and France, ranged from 6,900 to 7,400 years in age, and covered most of the LBK’s territorial spread.
Specifically, the team looked for the element strontium in teeth and measured the ratio of two isotopes, or types of the atom with slightly different weights. Strontium atoms enter the body in the water that we drink and the food we eat, and the ratio of the heavier isotope strontium-87 to the lighter isotope strontium-86 reflects the kind of soil and geological formations a person lived on, particularly as a child, when the tooth enamel was laid down. The strontium isotopes are increasingly used by archaeologists to track movements of populations.
Previous studies have shown that the kind of soil favored by European farmers, lowland sediments known as loess, has a slightly lower strontium-87/strontium-86 ratio than less-fertile areas such as upland hills made from granite or sandstone. Yet because of Europe’s variable landscape, in which fertile and non-fertile areas can be as close as several kilometers apart, the team relied more heavily on the degree of variation of strontium ratios among the skeletons in a burial site than on their absolute values.
The results of the study, published online today in the Proceedings of the National Academy of Sciences, suggest that men who were buried with adzes — thought to be an indication of higher social status — were more likely to have grown up on loess soils than men who were buried without adzes. For example, among 310 burials the team analyzed, 62 featured adzes. But only one of the 62 skeletons from the adze burials had a strontium ratio in its teeth typical of a non-loess landscape, whereas all of the others were consistent with growing up on loess. Moreover, the variation in strontium ratios between adze skeletons was significantly lower than the variation between non-adze skeletons, suggesting to Bentley and his co-workers that the adze skeletons came from one kind of landscape, most likely loess, while the others came from a variety of other landscapes.
A similarly striking pattern was seen when the team looked at the female skeletons, which made up 153 of the total 311 individuals analyzed. The variation in strontium ratios for females was significantly greater than for males, suggesting that a greater number of females than males had grown up in non-fertile areas. Moreover, the patterns in the male and female burials appeared in both earlier and later LBK settlements, suggesting that the patterns of social inequality were established from the beginning of the LBK period and did not develop gradually over time.
The team came to two main conclusions: First, some males had greater access to fertile soils than others, probably because they were the sons of farmers who had inherited access to the best land. And second, LBK societies were “patrilocal,” meaning that males tended to stay put in one place while females moved in from other areas to mate with them. A number of recent genetic studies have shown similar patterns among early European farmers. “The signatures from these skeletons reinforce other indications of male-dominated descent and even land inheritance,” Bentley says, adding that such social inequalities “only grew in extent and scale” over the course of history.
Read more at Wired Science
Huge Ancient Civilization's Collapse Explained
Ancient Egypt and Mesopotamia may be the best known of the first great urban cultures, but the largest was the Indus or Harappan civilization. This culture once extended over more than 386,000 square miles (1 million square kilometers) across the plains of the Indus River from the Arabian Sea to the Ganges, and at its peak may have accounted for 10 percent of the world population. The civilization developed about 5,200 years ago, and slowly disintegrated between 3,900 and 3,000 years ago — populations largely abandoned cities, migrating toward the east.
"Antiquity knew about Egypt and Mesopotamia, but the Indus civilization, which was bigger than these two, was completely forgotten until the 1920s," said researcher Liviu Giosan, a geologist at Woods Hole Oceanographic Institution in Massachusetts. "There are still many things we don't know about them."
Nearly a century ago, researchers began discovering numerous remains of Harappan settlements along the Indus River and its tributaries, as well as in a vast desert region at the border of India and Pakistan. Evidence was uncovered for sophisticated cities, sea links with Mesopotamia, internal trade routes, arts and crafts, and as-yet undeciphered writing.
"They had cities ordered into grids, with exquisite plumbing, which was not encountered again until the Romans," Giosan told LiveScience. "They seem to have been a more democratic society than Mesopotamia and Egypt — no large structures were built for important personalitiess like kings or pharaohs."
Like their contemporaries in Egypt and Mesopotamia, the Harappans, who were named after one of their largest cities, lived next to rivers.
"Until now, speculations abounded about the links between this mysterious ancient culture and its life-giving mighty rivers," Giosan said.
Now Giosan and his colleagues have reconstructed the landscape of the plain and rivers where this long-forgotten civilization developed. Their findings now shed light on the enigmatic fate of this culture.
"Our research provides one of the clearest examples of climate change leading to the collapse of an entire civilization," Giosan said.
The researchers first analyzed satellite data of the landscape influenced by the Indus and neighboring rivers. From 2003 to 2008, the researchers then collected samples of sediment from the coast of the Arabian Sea into the fertile irrigated valleys of Punjab and the northern Thar Desert to determine the origins and ages of those sediments and develop a timeline of landscape changes.
"It was challenging working in the desert — temperatures were over 110 degrees Fahrenheit all day long (43 degrees C)," Giosan recalled.
After collecting data on geological history, "we could reexamine what we know about settlements, what crops people were planting and when, and how both agriculture and settlement patterns changed," said researcher Dorian Fuller, an archaeologist with University College London. "This brought new insights into the process of eastward population shift, the change towards many more small farming communities, and the decline of cities during late Harappan times."
Some had suggested that the Harappan heartland received its waters from a large glacier-fed Himalayan river, thought by some to be the Sarasvati, a sacred river of Hindu mythology. However, the researchers found that only rivers fed by monsoon rains flowed through the region.
Previous studies suggest the Ghaggar, an intermittent river that flows only during strong monsoons, may best approximate the location of the Sarasvati. Archaeological evidence suggested the river, which dissipates into the desert along the dried course of Hakra valley, was home to intensive settlement during Harappan times.
"We think we settled a long controversy about the mythic Sarasvati River," Giosan said.
Initially, the monsoon-drenched rivers the researchers identified were prone to devastating floods. Over time, monsoons weakened, enabling agriculture and civilization to flourish along flood-fed riverbanks for nearly 2,000 years.
"The insolation — the solar energy received by the Earth from the sun — varies in cycles, which can impact monsoons," Giosan said. "In the last 10,000 years, the Northern Hemisphere had the highest insolation from 7,000 to 5,000 years ago, and since then insolation there decreased. All climate on Earth is driven by the sun, and so the monsoons were affected by the lower insolation, decreasing in force. This meant less rain got into continental regions affected by monsoons over time."
Eventually, these monsoon-based rivers held too little water and dried, making them unfavorable for civilization.
"The Harappans were an enterprising people taking advantage of a window of opportunity — a kind of "Goldilocks civilization," Giosan said.
Eventually, over the course of centuries, Harappans apparently fled along an escape route to the east toward the Ganges basin, where monsoon rains remained reliable.
"We can envision that this eastern shift involved a change to more localized forms of economy — smaller communities supported by local rain-fed farming and dwindling streams," Fuller said. "This may have produced smaller surpluses, and would not have supported large cities, but would have been reliable."
This change would have spelled disaster for the cities of the Indus, which were built on the large surpluses seen during the earlier, wetter era. The dispersal of the population to the east would have meant there was no longer a concentrated workforce to support urbanism.
Read more at Discovery News
May 28, 2012
It Took Earth Ten Million Years to Recover from Greatest Mass Extinction
Life was nearly wiped out 250 million years ago, with only 10 per cent of plants and animals surviving. It is currently much debated how life recovered from this cataclysm, whether quickly or slowly.
Recent evidence for a rapid bounce-back is evaluated in a new review article by Dr Zhong-Qiang Chen, from the China University of Geosciences in Wuhan, and Professor Michael Benton from the University of Bristol. They find that recovery from the crisis lasted some 10 million years, as explained May 27 in Nature Geoscience.
There were apparently two reasons for the delay, the sheer intensity of the crisis, and continuing grim conditions on Earth after the first wave of extinction.
The end-Permian crisis, by far the most dramatic biological crisis to affect life on Earth, was triggered by a number of physical environmental shocks -- global warming, acid rain, ocean acidification and ocean anoxia. These were enough to kill off 90 per cent of living things on land and in the sea.
Dr Chen said: "It is hard to imagine how so much of life could have been killed, but there is no doubt from some of the fantastic rock sections in China and elsewhere round the world that this was the biggest crisis ever faced by life."
Current research shows that the grim conditions continued in bursts for some five to six million years after the initial crisis, with repeated carbon and oxygen crises, warming and other ill effects.
Some groups of animals on the sea and land did recover quickly and began to rebuild their ecosystems, but they suffered further setbacks. Life had not really recovered in these early phases because permanent ecosystems were not established.
Professor Benton, Professor of Vertebrate Palaeontology at the University of Bristol, said: "Life seemed to be getting back to normal when another crisis hit and set it back again. The carbon crises were repeated many times, and then finally conditions became normal again after five million years or so."
Finally, after the environmental crises ceased to be so severe, more complex ecosystems emerged. In the sea, new groups, such as ancestral crabs and lobsters, as well as the first marine reptiles, came on the scene, and they formed the basis of future modern-style ecosystems.
Read more at Science Daily
Hubble Sees a Spiral Within a Spiral
Astronomers refer to the distinctive spiral-like bulge of galaxies such as ESO 498-G5 as disc-type bulges, or pseudobulges, while bright elliptical centers are called classical bulges. Observations from the Hubble Space Telescope, which does not have to contend with the distorting effects of Earth's atmosphere, have helped to reveal that these two different types of galactic centers exist. These observations have also shown that star formation is still going on in disc-type bulges and has ceased in classical bulges. This means that galaxies can be a bit like Russian matryoshka dolls: classical bulges look much like a miniature version of an elliptical galaxy, embedded in the center of a spiral, while disc-type bulges look like a second, smaller spiral galaxy located at the heart of the first -- a spiral within a spiral.
The similarities between types of galaxy bulge and types of galaxy go beyond their appearance. Just like giant elliptical galaxies, the classical bulges consist of great swarms of stars moving about in random orbits. Conversely, the structure and movement of stars within disc-type bulges mirror the spiral arms arrayed in a galaxy's disc. These differences suggest different origins for the two types of bulges: while classical bulges are thought to develop through major events, such as mergers with other galaxies, disc-type bulges evolve gradually, developing their spiral pattern as stars and gas migrate to the galaxy's center.
Read more at Science Daily
Teen Solves 350-Year-Old Math Problem
Sixteen-year-old Shouryya Ray, a boy of Indian origin attending school in Germany, cracked two particle dynamics theories. Ray's novel solutions can now help scientists calculate the flight path of a thrown ball and predict how it will strike and bounce off a wall, according to the International Business Times.
Ray was told by professors during a school field trip to Dresden University that the problem could not be solved. That notion didn't sit right with the Calcutta-born student.
"I just asked myself, 'Why not?'" Ray told Germany's Welt Online newspaper. "I didn't believe there couldn't be a solution."
According to Welt Online, Ray has been captivated by math since a very early age and was inspired by his father, Subhashis Ray, who works as a research assistant at the Technical University of Freiburg. His father began teaching Ray calculus at the tender age of six.
Ray's family moved to Germany when he was 12. Ray didn't speak German when they first moved to Germany and now he is fluent in the language.
As for his future career, Ray is debating whether to study math or physics when he moves on to college.
From Discovery News
NASA Wanted Astronauts to View Venus Up-Close
The mission was developed under the Apollo Applications Program (AAP) that was designed to build on and apply Apollo-era technology to greater goals in space. Out of the AAP NASA hoped to see Earth orbiting laboratories, research stations on the moon, and manned interplanetary missions. In 1967, this was America’s future in space.
One of the interplanetary targets was Venus. After visiting the planet with the unmanned Mariner 2 spacecraft in 1962, NASA learned that the planet lacks a strong magnetic field, has an extremely hot surface generated in the lower atmosphere or surface, and that the cosmic radiation in the interplanetary space was survivable. NASA also learned that it was worth going back. There was undoubtedly more to Venus locked under its thick cloud cover.
To get a crew there, NASA would use a revised Apollo spacecraft. Like the lunar missions, it was a tripartite design composed of a Command and Service Module (CSM), and Environmental Support Module (ESM), and a third habitable section. Here’s how the mission was designed to play out.
A three-man crew, nestled in the CM, would launch on a Saturn V. The CSM would perform the same functions it did during the Apollo lunar missions: its onboard computer would serve as the primary guidance and navigation system, provide the main reaction control, and act as the principle telemetry and communications link with mission control. Really, the mission would be a simple of matter of engineers rewriting the computer’s commands to send the crew to Venus instead of the moon. The hard part is keeping them alive and well during the 400 day mission. This is where the other modules come into play.
With no purpose for a Lunar Module on a Venus flyby, the spidery spacecraft would be swapped out for the larger ESM. Once in Earth orbit, the crew would separate the CSM from the rest of the spacecraft, turn around, and dock with the ESM. Then they could open the hatch and transfer between the vehicles. The ESM was designed as the principle experiment bay on the mission and would provide long term life support and environmental control to the whole spacecraft configuration.
With the CSM and ESM docked, the Saturn V’s upper SIV-B stage would fire and send the whole thing towards Venus. But instead of jettisoning the spent rocket stage, the crew would re-purpose it -- neither of the other two module gave them a comfortable living space. In the ESM the astronauts would have everything they’d need to refurbish the rocket stage and turn it into their main habitable module and recreational space. Solar panels lining the outside would provide power to the whole spacecraft.
The mission planned to launch sometime during the month-long window between Oct. 31 and Nov. 30 1973; the dates offered a quick transit to Venus and the year was expected to be a quiet one for solar activity, minimizing the crew’s exposure to dangerous solar radiation.
The outbound leg of the mission was expected to last 123 days. The crew would arrive at Venus sometime in the month of March 1974 and pass just 3,340 nautical miles -- about 3,834 statute miles -- above the surface as they whipped around to begin the 273 day trip back to Earth. The mission would end in a splashdown sometime in December 1974.
Read more at Discovery News
May 27, 2012
New Genetic Method Developed to Pinpoint Individuals' Geographic Origin
Now, a team of researchers from the UCLA Henry Samueli School of Engineering and Applied Science, UCLA's Department of Ecology and Evolutionary Biology and Israel's Tel Aviv University has developed an innovative approach to the study of genetic diversity called spatial ancestry analysis (SPA), which allows for the modeling of genetic variation in two- or three-dimensional space.
Their study is published online this week in the journal Nature Genetics.
With SPA, researchers can model the spatial distribution of each genetic variant by assigning a genetic variant's frequency as a continuous function in geographic space. By doing this, they show that the explicit modeling of the genetic variant frequency -- the proportion of individuals who carry a specific variant -- allows individuals to be localized on a world map on the basis of their genetic information alone.
"If we know from where each individual in our study originated, what we observe is that some variation is more common in one part of the world and less common in another part of the world," said Eleazar Eskin, an associate professor of computer science at UCLA Engineering. "How common these variants are in a specific location changes gradually as the location changes.
"In this study, we think of the frequency of variation as being defined by a specific location. This gives us a different way to think about populations, which are usually thought of as being discrete. Instead, we think about the variant frequencies changing in different locations. If you think about a person's ancestry, it is no longer about being from a specific population -- but instead, each person's ancestry is defined by the location they're from. Now ancestry is a continuum."
The team reports the development of a simple probabilistic model for the spatial structure of genetic variation, with which they model how the frequency of each genetic variant changes as a function of the location of the individual in geographic space (where the gene frequency is actually a function of the x and y coordinates of an individual on a map).
"If the location of an individual is unknown, our model can actually infer geographic origins for each individual using only their genetic data with surprising accuracy," said Wen-Yun Yang, a UCLA computer science graduate student.
"The model makes it possible to infer the geographic ancestry of an individual's parents, even if those parents differ in ancestry. Existing approaches falter when it comes to this task," said UCLA's John Novembre, an assistant professor in the department of ecology and evolution.
SPA is also able to model genetic variation on a globe.
"We are able to also show how to predict the spatial structure of worldwide populations," said Eskin, who also holds a joint appointment in the department of human genetics at the David Geffen School of Medicine at UCLA. "In just taking genetic information from populations from all over the world, we're able to reconstruct the topology of the global populations only from their genetic information."
Using the framework, SPA can also identify loci showing extreme patterns of spatial differentiation.
"These dramatic changes in the frequency of the variants potentially could be due to natural selection," Eskin said. "It could be that something in the environment is different in different locations. Let's say a mutation arose that has some advantageous property in a certain environment. So you can imagine then that a kind of force for genetic selection would make this mutation more common in that environment."
Read more at Science Daily
It's in the Genes: Research Pinpoints How Plants Know When to Flower
Determining the proper time to flower, important if a plant is to reproduce successfully, involves a sequence of molecular events, a plant's circadian clock and sunlight.
Understanding how flowering works in the simple plant used in this study -- Arabidopsis -- should lead to a better understanding of how the same genes work in more complex plants grown as crops such as rice, wheat and barley, according to Takato Imaizumi, a University of Washington assistant professor of biology and corresponding author of a paper in the May 25 issue of the journal Science.
"If we can regulate the timing of flowering, we might be able to increase crop yield by accelerating or delaying this. Knowing the mechanism gives us the tools to manipulate this," Imaizumi said. Along with food crops, the work might also lead to higher yields of plants grown for biofuels.
At specific times of year, flowering plants produce a protein known as FLOWERING LOCUS T in their leaves that induces flowering. Once this protein is made, it travels from the leaves to the shoot apex, a part of the plant where cells are undifferentiated, meaning they can either become leaves or flowers. At the shoot apex, this protein starts the molecular changes that send cells on the path to becoming flowers.
Changes in day length tell many organisms that the seasons are changing. It has long been known that plants use an internal time-keeping mechanism known as the circadian clock to measure changes in day length. Circadian clocks synchronize biological processes during 24-hour periods in people, animals, insects, plants and other organisms.
Imaizumi and the paper's co-authors investigated what's called the FKF1 protein, which they suspected was a key player in the mechanism by which plants recognize seasonal change and know when to flower. FKF1 protein is a photoreceptor, meaning it is activated by sunlight.
"The FKF1 photoreceptor protein we've been working on is expressed in the late afternoon every day, and is very tightly regulated by the plant's circadian clock," Imaizumi said. "When this protein is expressed during days that are short, this protein cannot be activated, as there is no daylight in the late afternoon. When this protein is expressed during a longer day, this photoreceptor makes use of the light and activates the flowering mechanisms involving FLOWERING LOCUS T. The circadian clock regulates the timing of the specific photoreceptor for flowering. That is how plants sense differences in day length."
This system keeps plants from flowering when it's a poor time to reproduce, such as the dead of winter when days are short and nights are long.
The new findings come from work with the plant Arabidopsis, a small plant in the mustard family that's often used in genetic research. They validate predictions from a mathematical model of the mechanism that causes Arabidopsis to flower that was developed by Andrew Millar, a University of Edinburgh professor of biology and co-author of the paper.
"Our mathematical model helped us to understand the operating principles of the plants' day-length sensor," Millar said. "Those principles will hold true in other plants, like rice, where the crop's day-length response is one of the factors that limits where farmers can obtain good harvests. It's that same day-length response that needs controlled lighting for laying chickens and fish farms, so it's just as important to understand this response in animals.
"The proteins involved in animals are not yet so well understood as they are in plants but we expect the same principles that we've learned from these studies to apply."
Read more at Science Daily
Subscribe to:
Posts (Atom)