Friday 25 January 2013

Quadruple helix' DNA seen in human cells


25 January 2013

Quadruple helix' DNA seen in human cells


'Quadruple helix' DNA seen in human cells

A representation of the four-stranded structure (L) and fluorescent markers reveal its presence inside cells (R)  A representation of the four-stranded structure (L) with fluorescent markers revealing its presence inside cells (R)

Cambridge University scientists say they have seen four-stranded DNA at work in human cells for the first time.
The famous "molecule of life", which carries our genetic code, is more familiar to us as a double helix.
But researchers tell the journal Nature Chemistry that the "quadruple helix" is also present in our cells, and in ways that might possibly relate to cancer.
They suggest that control of the structures could provide novel ways to fight the disease.
"The existence of these structures may be loaded when the cell has a certain genotype or a certain dysfunctional state," said Prof Shankar Balasubramanian from Cambridge's department of chemistry.
"We need to prove that; but if that is the case, targeting them with synthetic molecules could be an interesting way of selectively targeting those cells that have this dysfunction," he told BBC News.
Tag and track It will be exactly 60 years ago in February that James Watson and Francis Crick famously burst into the pub next to their Cambridge laboratory to announce the discovery of the "secret of life". 
What they had actually done was describe the way in which two long chemical chains wound up around each other to encode the information cells need to build and maintain our bodies. 
Today, the pair's modern counterparts in the university city continue to work on DNA's complexities.
Balasubramanian's group has been pursuing a four-stranded version of the molecule that scientists have produced in the test tube now for a number of years.
It is called the G-quadruplex. The "G" refers to guanine, one of the four chemical groups, or "bases", that hold DNA together and which encode our genetic information (the others being adenine, cytosine, and thymine).
The G-quadruplex seems to form in DNA where guanine exists in substantial quantities. 
And although ciliates, relatively simple microscopic organisms, have displayed evidence for the incidence of such DNA, the new research is said to be the first to firmly pinpoint the quadruple helix in human cells.
'Funny target' The team, led by Giulia Biffi, a researcher in Balasubramaninan's lab, produced antibody proteins that were designed specifically to track down and bind to regions of human DNA that were rich in the quadruplex structure. The antibodies were tagged with a fluorescence marker so that the time and place of the structures' emergence in the cell cycle could be noted and imaged.
This revealed the four-stranded DNA arose most frequently during the so-called "s-phase" when a cell copies its DNA just prior to dividing.
Prof Balasubramaninan said that was of key interest in the study of cancers, which were usually driven by genes, or oncogenes, that had mutated to increase DNA replication.
If the G-quadruplex could be implicated in the development of some cancers, it might be possible, he said, to make synthetic molecules that contained the structure and blocked the runaway cell proliferation at the root of tumours.
"We've come a long way in 10 years, from simple ideas to really seeing some substance in the existence and tractability of targeting these funny structures," he told the BBC.
"I'm hoping now that the pharmaceutical companies will bring this on to their radar and we can perhaps take a more serious look at whether quadruplexes are indeed therapeutically viable targets."
Prof Shankar Balasubramanian Prof Shankar Balasubramanian in front of a painting by artist Annie Newman that represents quadruplex DNA



Small dogs originate in Middle East, says gene study

Small dogs originate in Middle East, says gene study

Chihuahua
Small dogs may have evolved from the Middle Eastern grey wolf
Small dogs may all originate from the Middle East, according to research from the University of California.
A study published in the journal BioMed Central found a gene found in small dogs, IGF1, is closely related to one found in Middle Eastern wolves.
Archaeologists have found the remains of small dogs dating back 12,000 years in the region.
In Europe, older remains have been uncovered, dating from 31,000 years ago, but these are from larger dogs.
"Because all small dogs possess this variant of IGF1, it probably arose early in their history," said Dr Melissa Gray from the University of California, Los Angeles.
The team of researchers took samples from grey wolf populations around the world.

 Maybe they can have a better understanding of the history of their pets 
Dr Melissa Gray
"We have a couple of individuals from North America, from Yellowstone and Alaska, several from the Middle East, Israel, Iran, India, China, Russia, Italy, Spain, Belarus and Belgium," explained Dr Gray.
The study says the similarity between the variant found in small dogs and that in the Middle Eastern grey wolf shows small size probably originated as a result of the wolf's domestication.
The scientists believe people may have preferred smaller dogs because they were easier to house in farming societies where space was at a premium.
Animals often become smaller as a result of domestication and the trend can be seen in cattle, pigs and goats.
Dr Gray believes the results could be useful for dog breeders: "Because we have this gene and that it affects body size it could possibly be used as a way to breed for small body size."
And she hopes small dog owners around the world will find the results interesting. "Maybe they can have a better understanding of the history of their pets and where they came from and how they likely dispersed out from the region."

Dog evolved 'on the waste dump'


Dog evolved 'on the waste dump'

Grey wolfWolves that coped best with cereals in their diet may be part of the story of domestication

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Anyone who owns a dog knows that it will rummage around in the kitchen bin looking for food, given half a chance.
But this annoying behaviour may have a more profound undercurrent than we realise, according to scientists.
A new study of dog genetics reveals numerous genes involved in starch metabolism, compared with wolves.
It backs an idea that some dogs emerged from wolves that were able to scavenge and digest the food waste of early farmers, the team tells Nature journal.
No-one knows precisely when or how our ancestors became so intimately connected with dogs, but the archaeological evidence indicates it was many thousands of years ago.
One suggestion is that the modern mutt emerged from ancient hunter-gatherers' use of wolves as hunting companions or guards.
But another opinion holds that domestication started with wolves that stole our food leftovers and eventually came to live permanently around humans as a result.
"This second hypothesis says that when we settled down, and in conjunction with the development of agriculture, we produced waste dumps around our settlements; and suddenly there was this new food resource, a new niche, for wolves to make use of, and the wolf that was best able to make use of it became the ancestor of the dog," explained Erik Axelsson from Uppsala University.
"So, we think our findings fit well with this theory that the dog evolved on the waste dump," he told BBC News.
When did dogs stop being wolves
Dr Axelsson and colleagues examined the DNA of more than 50 modern dogs from breeds as diverse as the cocker spaniel and the German shepherd. They then compared their generic genetic information with those of 12 wolves taken from across the world.
The Swedish-US team scanned the DNA sequences of the two types of canid for regions of major difference. These would be locations likely to contain genes important in the rise of the domesticated dog.
Axelsson's group identified 36 such regions, carrying a little over a hundred genes. The analysis detected the presence of two major functional categories - genes involved in brain development and starch metabolism.
In the case of the latter, it seems dogs have many more genes that encode the enzymes needed to break down starch, something that would have been advantageous in an ancestor scavenging on the discarded wheat and other crop products of early farmers.
Girl relaxes with dogDomestication may have forced dogs into a permanent state of puppyhood
"Wolves also have these genes but they don't use them as efficiently as dogs," said Dr Axelsson.
"When we look at the wolf genome, we only see one copy of the gene [for the amylase enzyme] on each chromosome. When we look at the dog genome, we see a range from two to 15 copies; and on average a dog carries seven copies more than the wolf.
"That means the dog is a lot more efficient at making use of the nutrition in starch than the wolf."
As far as the brain development genes are concerned, these probably reflect some of the behavioural differences we now see in the two canids.
The dog is a much more docile creature, the likely consequence of early humans preferentially working with animals they found easier to tame.
"Previous experiments have indicated that when you select for a reduction in aggressiveness, you obviously get a tamer animal but you also get an animal that retains juvenile characteristics much longer during development, sometimes into adulthood," said Dr Axelsson.
This might go some way to explaining the oft-repeated observation that dogs are permanently stuck in a kind of puppyhood.
Open debate
The study of the origin of dogs remains, in many ways, a puzzling field.
Fossil evidence suggests some populations could have been around tens of thousands of years ago, long before the emergence of agriculture. Some researchers have tried to use the regular rate at which error patterns appear in dog DNA as a kind clock to time their rise, but this has produced contradictory results.
One confounding issue might be that domestication happened more than once.
Dr Carles Vila, from the Conservation and Evolutionary Genetics Group at the Donana Biological Station in Seville, Spain, said the debate was wide open.
"I think that modern dogs derived from multiple wolf populations," he observed.
"It could be that dog domestication started once with some animals staying with humans which were then regularly back-crossed with wolves and that could have the same effect. But there could have been completely independent domestications. What is clear is that the number of bone remains is very rare more than 14,000 years ago."
Jonathan.Amos-INTERNET@bbc.co.uk and follow me on Twitter:@BBCAmos

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Tuesday 15 January 2013

Genes link Australia with India


Ancient migration: Genes link Australia with India

Aboriginal manResearchers compared the DNA of Aboriginal Australians with Indians' genetic material

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Australia experienced a wave of migration from India about 4,000 years ago, a genetic study suggests.
It was thought the continent had been largely isolated after the first humans arrived about 40,000 years ago until the Europeans moved in in the 1800s.
But DNA from Aboriginal Australians revealed there had been some movement from India during this period.
The researchers believe the Indian migrants may have introduced the dingo to Australia.
In the Proceedings of the National Academy of Sciences, they say that the fossil record suggests the wild dogs arrived in Australia at around the same time.
They also suggest that Indians may have brought stone tools called microliths to their new home.
Ancient origins
"For a long time, it has been commonly assumed that following the initial colonization, Australia was largely isolated as there wasn't much evidence of further contact with the outside world," explained Prof Mark Stoneking, from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.
DingoDingoes first appeared in Australia at about the same time as the Indians
"It is one of the first dispersals of modern humans - and it did seem a bit of a conundrum that people who got there this early would have been so isolated."
To study the early origins of Australia's population, the team compared genetic material from Aboriginal Australians with DNA from people in New Guinea, South East Asia and India.
By looking at specific locations, called genetic markers, within the DNA sequences, the researchers were able to track the genes to see who was most closely related to whom.
They found an ancient genetic association between New Guineans and Australians, which dates to about 35,000 to 45,000 years ago. At that time, Australia and New Guinea were a single land mass, called Sahul, and this tallies with the period when the first humans arrived.

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It is strongly suggestive that microliths, dingo and the movement of people were all connected”
Mark StonekingMax Planck Institute for Evolutionary Anthropology
But the researchers also found a substantial amount of gene flow between India and Australia.
Prof Stoneking said: "We have a pretty clear signal from looking at a large number of genetic markers from all across the genome that there was contact between India and Australia somewhere around 4,000 to 5,000 years ago."
He said the genetic data could not establish the route the Indians would have taken to reach the continent, but it was evidence that Australia was not as cut off as had been assumed.
"Our results show that there were indeed people that made a genetic contribution to Australians from India," Prof Stoneking explained.
The researchers also looked at fossils and other archaeological discoveries that date to this period.
They said changes in tool technology and new animals could possibly be attributed to the new migrants.
Prof Stoneking said: "We don't have direct evidence of any connection, but it strongly suggestive that microliths, dingo and the movement of people were all connected."

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Thursday 10 January 2013

Giant squid


Giant squid captured on video in ocean depths

In this image made from video recorded in the summer of 2012, provided by NHK and Discovery Channel, a giant squid takes bait in the deep sea off Chichi island, Japan. (AP/ NHK/NEP/Discovery Channel )
In this image made from video recorded in the summer of 2012, provided by NHK and Discovery Channel, a giant squid takes bait in the deep sea off Chichi island, Japan. (AP/ NHK/NEP/Discovery Channel)
After years of searching, scientists and broadcasters say they have captured video images of a giant squid in its natural habitat deep in the ocean for the first time.
The three-meter (nine-foot) invertebrate was filmed from a manned submersible during one of 100 dives in the Pacific last summer in a joint expedition by Japanese public broadcaster NHK, Discovery Channel and Japan's National Museum of Nature and Science.
NHK released photographs of the giant squid this week ahead of Sunday's show about the encounter. The Discovery Channel will air its program on Jan. 27.
The squid, which was inexplicably missing its two longest tentacles, was spotted in waters east of Chichi Island about 1,000 kilometers (600 miles) south of Tokyo, NHK said. The crew followed it to a depth of 900 meters (2,950 feet).
Little is known about the creature because its harsh environment makes it difficult for scientists to conduct research. Specimens have washed ashore on beaches but never before have been filmed in their normal habitat deep in the ocean, researchers say.
Japanese zoologist Tsunemi Kubodera, who was on board the submersible at the time of the encounter, was able to lure the giant squid with a one-meter (three-foot) -long diamond squid.
All the lights from the submersible were turned off while they waited. At a depth of 640 meters (2,100 feet), the giant squid appeared and wrapped its arms around the bait, eating it for over 20 minutes before letting go.
"What we were able to gain from this experience was the moment of the giant squid attacking its prey — we were able record that," said Kubodera, who has been researching the giant squid since 2002.
Other scientists involved in the expedition this summer, which logged 400 hours of dives, were American oceanographer and marine biologists Edith Widder and Steve O'Shea from New Zealand.
NHK said a high-definition camera was developed for the project that could operate deep in the ocean and used a special wavelength of light invisible to the giant squid's sensitive eyes.
Kubodera said scientific research, technology and the right lure all came together to make the encounter possible, and that this case will shed more light on deep-sea creatures going forward.
After more than a decade of going out to sea in search of the giant squid, he relished the moment he came face-to-face with it.
"It appeared only once, out of 100 dives. So perhaps, after over 10 years of some kind of relationship I've built with the giant squids, I feel, perhaps, it was the squid that came to see me."
___
Associated Press video journalist Emily Wang contributed to this report

3,000 years old Ancient tombs unearthed in Egyptian city of Luxor


Ancient tombs unearthed in Egyptian city of Luxor

Jars used to preserve human organs found under mortuary temple in Egypt. 10 Jan 2013Jars were used to contain the liver, lungs, stomach and intestines of the deceased

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Italian archaeologists have unearthed tombs in the southern Egyptian city of Luxor that are more than 3,000 years old.
Egypt's antiquities ministry says the tombs were found under the mortuary temple of the Pharoah Amenhotep II, who reigned from 1427 BC to 1401 BC.
The temple is located on the western bank of the River Nile.
The ministry said remains of wooden sarcophaguses and human bones were found inside the tombs.
Jars used to preserve the liver, lungs, stomach and intestines of the deceased were also found, decorated with images of the four sons of the god Horus.
The figures - which have the heads of a human, a baboon, a jackal and a falcon - were believed to help the soul find its way to heaven.
Wafaa Elsaddik, a professor of Egyptology, told the BBC the find was significant because it showed that temples were not just used for worship, but for burial as well.
She said the jars were of very good quality which suggested that the tombs had belonged to wealthy people.

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Saturday 5 January 2013

'oldest cave art'


21 June 2012

'oldest cave art'


Bristol researchers removing samples for dating from Tito Bustillo Cave, Spain Bristol researchers removing samples for dating from Tito Bustillo Cave
Red discs The El Castillo Cave has numerous red discs on its walls. One was dated to 40,800 years ago

Red dot becomes 'oldest cave art'

A look inside the Altamira Cave in northern Spain
Red dots, hand stencils and animal figures represent the oldest examples yet found of cave art in Europe.
The symbols on the walls at 11 Spanish locations, including the World Heritage sites of Altamira, El Castillo and Tito Bustillo have long been recognised for their antiquity.
But researchers have now used refined dating techniques to get a more accurate determination of their ages.
One motif - a faint red dot - is said to be more than 40,000 years old.
"In Cantabria, [in] El Castillo, we find hand stencils that are formed by blowing paint against the hands pressed against the wall of a cave," explained Dr Alistair Pike from Bristol University, UK, and the lead author on a scholarly paper published in the journal Science.
"We find one of these to date older than 37,300 years on 'The Panel of Hands', and very nearby there is a red disc made by a very similar technique that dates to older than 40,800 years.
"This now currently is Europe's oldest dated art by at least 4,000 years," he told reporters. It is arguably also the oldest reliably dated cave art anywhere in the world.
The team arrived at the ages by examining the calcium carbonate (calcite) crusts that had formed on top of the paintings.
This material builds up in the exact same way that stalagmites and stalactites form in a cave.
In the process, the calcite incorporates small numbers of naturally occurring radioactive uranium atoms. These atoms decay into thorium at a very precise rate through the ages, and the ratio of the two different elements in any sample can therefore be used as a kind of clock to time the moment when the calcite crust first formed.
Uranium-thorium dating has been around for decades, but the technique has now been so refined that only a tiny sample is required to get a good result.
This enabled the team to take very thin films of deposits from just above the paint pigments; and because the films were on top, the dates they gave were minimum ages - that is, the paintings had to be at least as old as the calcite deposits, and very probably quite a bit older.
The oldest dates coincide with the first known immigration into Europe of modern humans (Homo sapiens). Before about 41,000 years ago, it is their evolutionary cousins, the Neanderthals (Homo neanderthalensis), who dominate the continent.
Dr Pike's and colleagues' work therefore raises some intriguing questions about who might have authored the markings.
If anatomically modern humans were responsible then it means they engaged in the activity almost immediately on their arrival in Europe.
If Neanderthals were the artisans, it adds another layer to our understanding of their capabilities and sophistication.
Hand stencils The Panel of Hands: Produced by blowing paint over a hand pressed against the wall
The great antiquity of the paintings leads co-author Joao Zilhao, a research professor at ICREA, University of Barcelona, to think the Neanderthals produced the motifs. Finding even older paintings than the red dot at El Castillo might confirm that "gut feeling", he said.
"There is a strong chance that these results imply Neanderthal authorship," Prof Zilhao explained.
"But I will not say we have proven it because we haven't, and it cannot be proven at this time.
"What we have to do now is go back, sample more and find out whether we can indeed get dates older than 42, 43, 44,000.
"There is already a sampling programme going on. We have samples from more sites in Spain, from sites in Portugal and from other caves in Western Europe and so eventually we will be able to sort it out."
Tracing the origins of abstract throught and behaviours, and the rate at which they developed, are critical to understanding the human story.
The use of symbolism - the ability to let one thing represent another in the mind - is one of those traits that set our animal species apart from all others.
It is what underpins artistic endeavour and also the use of language.