Now, for the first time, a team of researchers from The Rockefeller University, Brookhaven National Laboratory, and Stony Brook University has revealed that vital complex molecular architecture.
And to their surprise, it does not look as they had expected. ur finding goes against decades of textbook drawings of
says Michael Oonnell, Anthony and Judith Evnin Professor, head of Rockefeller Laboratory of DNA Replication and a Howard hughes medical institute investigator.
and examining its shape in the electron microscope powerful device used to study protein structures, and a specialty of co-author Huilin Li, a molecular biologist at Brookhaven National Laboratory and Stony Brook University.
The pictures Li and members of his lab captured were the first ever made of a complete replisome from any type of cell.
A link to epigenetics To identify which polymerase was at the top of the helicase,
the team enlisted the help of co-authors postdoc Yi Shi and Brian Chait, the Camille and Henry Dreyfus Professor at Rockefeller and head of the Laboratory of Mass Spectrometry and Gaseous Ion Chemistry.
Previous work has shown that Pol-e binds nucleosomes, and it may be that while riding atop the helicase,
Oonnell suggests. hanges to nucleosomes carry epigenetic information that instructs different cells to become the different tissues of the body,
and other organs during embryonic development, Oonnell says. o we can speculate that Pol-e interaction with nucleosomes could play a role in assigning different epigenetic identities to the two new daughter cells after cell division,
For the first time, scientists have identified a protein inside blood vessels found at the invasive edge of brain tumours highlighting the area from where cancer is most likely to spread.
Mapping this inflammation gives scientists a more complete picture of the cancer. The scientists have developed a special dye that recognises
Professor Nicola Sibson, study author and Cancer Research UK scientist at The University of Oxford, said:
f we can map the edge of the tumour, surgery and radiotherapy often fail to remove aggressive tumour cells
and the brain tumour can grow back. his research shows that we can improve imaging of brain tumours,
which could help both surgeons and radiotherapists with more effective treatment. Professor Charlie Swanton, NCRI chair and Cancer Research UK scientist at the Francis Crick Institute, said:
rain tumours are very difficult to treat and take the lives of too many patients each year.
and spread has potential to really help doctors treat patients and help save more lives.
Harpal Kumar, Cancer Research UK chief executive, said: rain cancers continue to have very poor survival rates,
which is why research into how to treat them is a top priority for Cancer Research UK.
Being able to delineate the edges of brain tumours is an exciting step towards better surgery and radiotherapy for patients.
The holy grail would be to be able to completely remove brain tumours with the help of this new imaging technique reducing recurrence of the disease
and saving more lives. i
#Whopping Galaxy cluster Spotted with Help of NASA Telescopes Astronomers have discovered a giant gathering of galaxies in a very remote part of the universe, thanks to NASA Spitzer space telescope and Wide-field Infrared Survey Explorer (WISE.
said Anthony Gonzalez of the University of Florida in Gainesville, lead author of a new study published in the Oct 20 issue of the Astrophysical Journal Letters.
Using data from the Combined Array for Research in Millimeter-wave Astronomy (CARMA) telescopes near Owens Valley in California,
we can start to investigate how galaxies evolved in these extreme environments, said Gonzalez n
#Breeding higher yielding crops by increasing sugar import into seeds Once a mother plant releases its embryos to the outside world,
they have to survive on their own without family protection. To ensure successful colonization by these vulnerable creatures,
the mother plant provides the embryo with a backpack full of energy, called the endosperm. Since, over time, the only plants that will survive are those that reproduce
and compete successfully, the mother plant whole life is dedicated to producing sugars in its leaves,
The sugars are manufactured in the leaves when the plant turns the Sun energy into chemical energy
and then transported to the seeds. The amount of sugars that fill a seed directly determines the seed size.
A team of scientists led by Carnegie Wolf Frommer has discovered now that a sugar-transport protein in maize
and shows genome changes that indicate domestication by humans. The new research is published in Nature Genetics.
The plant endosperm has been an important factor in the establishment of a mutualistic relationship with humanso facilitate their survival and spread,
crop plants have evolved larger backpacks to ensure continued utility to humans. Without knowing which gene variants were contributing useful properties,
which happened with all of our crop plants as wild plants were converted into more and more useful and nutritious versions.
The ancestors of the modern maize planted today across large acreages in the U s . and worldwide had much smaller endosperms.
more sugar-filled seeds such as maize kernels were more attractive to human cultivators, due to their nutritive value and their ability to produce sturdier seedlings.
But a direct link between the biochemistry of the seed-filling processes and domestication had remained long elusive.
and transporting sugars from the leaves to other tissues. They also discovered that SWEETS make plants susceptible to hijacking by pathogens that steal plant energy supplies before they can be transported to the seeds.
How was this remarkable new discovery made? Several labs contributed. Frommer team analyzed maize genes involved in sugar-related processes to find ones that were seed urned onduring development.
They found 16 candidates, and among them one was clearly outstanding. The gene SWEET4C, which encodes a sugar transporter protein in maize,
was shown to be expressed specifically in the maize seed by the group of Prem Chourey at University of Florida,
and had evidence of selection due to domestication. The evidence that the SWEET4C gene was selected during domestication was discovered by the team of Jeff Ross-Ibarra at UC Davis,
while comparing SWEET4 sequences from modern maize against its wild ancestor Teosinte. If variation of the sequence of a specific gene is reduced greatly in modern versions
between 10 and 17 days after the seed is pollinated. e believe that as early farmers selected larger seeds to eat and plant,
such as in the mutant lines provided by the Uniformmu resource (Don Mccarty and Karen Koch at the University of Florida),
Gratifyingly, the importance of the study goes beyond maize yield. The authors found that the corresponding gene in rice was also critical for seed filling
and showed independent signs of selection by farmers and breeders. ur work indicates that SWEET4 could be a promising target for engineering varieties of maize,
rice and other crops, said Bing Yang from Iowa State university, whose team performed all the rice studies.
When scientists develop a new drug, they need to work with the pharmaceutical industry to perform extensive tests to ultimately bring it to the consumers.
Similarly plant scientists need to work with industry to explore the full potential of a discovery.
#Tiny Drones That Navigate with Insect Eyes A tiny artificial eye inspired by the vision systems of insects could help small flying drones navigate their surroundings well enough to avoid collisions while buzzing around in confined,
cluttered spaces key step in making these small autonomous flying vehicles practical. An emerging class of very small flying drones has taken off in public
and private research labs in recent years (see obotic Insect Takes Off. These mini drones could be valuable in spying and surveillance;
they might also be useful for things like monitoring disaster areas or delivering supplies to humans.
But there remains a lot of work to be done toward developing miniature navigation systems, particularly for confined spaces.
The new sensor his group recently unveiled weighs only two milligrams and takes up only two cubic millimeters,
and can detect motion in conditions ranging from a poorly lit room to very bright sunlight outdoorshree times faster than fast flying insects,
Algorithms for processing the signals have already been developed and they can be programmed into small chips to compute things like distance to objects or the time until a potential collision.
One focus of the group current work is integrating this system into ery small aerial platformslike the foldable quadrotor the lab recently developed.
The challenge, says Floreano, will be to combine multiple artificial eyes into configurations that allow the drone to ee all aroundand avoid collisions,
stabilize its flying position, land, and take off. He says the elementary eyes are suited particularly for drones that weigh 50 grams or less,
and which cannot lift a payload larger than a few grams. The sensor could be useful for other things besides flying robots.
For demonstration the group created what Floreano calls ision tape, a flexible patch containing many artificial eyes.
including other kinds of robots, vehicles, and even furniture and clothing, he says a
#Google Bids to Make its Sideshows into Main Attractions Google founders Larry page and Sergey Brin seem determined to prove they gave the world more than a great advertising business.
For all the self-driving cars, AI breakthroughs, and Internet balloons, ads on Web pages and inside apps provide over 90 percent of their company revenue.
But a major reorganization of Page and Brin company today puts their most technologically ambitiousnd in business terms,
embryonicrojects on an equal footing with their profit-generating machine. Googleomprising the search engine, ad business, Youtube,
and Android mobile softwares now just one of many subsidiaries of a conglomerate called Alphabet.
The CEO of the new Google is Sundar Pichai an executive who was most recently in charge of Google main products
and previously led work on the Chrome browser and operating system and Android. Alphabet other subsidiariest not clear just how many will bere a grab bag of attempts to shake up the world using new technologies.
They include the antiaging company Calico; a life sciences division, working on electronic contact lenses; the research lab Google X, where oonshotprojects include self-driving cars
and delivering Wireless internet via stratospheric balloons; and Nest, which sells connected home devices and is trying to reinvent the face-worn computer Google glass.
Larry page (as of today Alphabet CEO; Brin is described president Alphabet as ostly a collection of companiesin a blog post announcing the reorganization today.
Right nownd probably for a whilene of those ompanieswill be pulling the weight of all the rest.
But the message seems to be that ideas like self-driving cars and defeating aging could become as successful and influential as Google online services are today.
How long that will take is anybody guess. Calico looks to be the mooniest of moonshots.
Nest generates revenue today, but its thermostat and smoke detector likely don sell in huge volumes.
And although Google X Loon balloon project for Internet access is at the point of testing with wireless carriers
it still has far to go before real deployment. We can probably expect Alphabet to spawn more subsidiaries before any of those we know today make a major mark on the world.
Many projects inside the Google X lab, such as the self-driving car, are about as distinct and mature as other Alphabet subsidiaries named today, for example.
And in his post today Page said that he expected his new company to make it easier to get ore ambitious things done,
and to spend more on long-term projects t
#Researchers Smash Records with Pig-to-Primate Organ transplants A biotech company is genetically engineering pigs so that their organs might work in people.
With the financial aid of a biotechnology executive whose daughter may need a lung transplant, U s. researchers have been shattering records in xenotransplantation,
or between-species organ transplants. The researchers say they have kept a pig heart alive in a baboon for 945 days
and also reported the longest-ever kidney swap between these species, lasting 136 days. The experiments used organs from pigs umanizedwith the addition of as many as five human genes
a strategy designed to stop organ rejection. The GM pigs are being produced in Blacksburg, Virginia, by Revivicor, a division of the biotechnology company United Therapeutics.
That company founder and co-CEO, Martine Rothblatt, is noted a futurist who four years ago began spending millions to supply researchers with pig organs
and has quickly become the largest commercial backer of xenotransplantation research. Rothblatt says her goal is to create n unlimited supply of transplantable organsand to carry out the first successful pig-to-human lung transplant within a few years.
One of her daughters has a usually fatal lung condition called pulmonary arterial hypertension. In addition to GM pigs
her company is carrying out research on tissue-engineered lungs and cryopreservation of organs. ee turning xenotransplantation from
what looked like a kind of Apollo-level problem into just an engineering task, she says.
Some researchers agree with Rothblatt that the latest results mean pig-to-human transplants are plausible. think it possible;
it should be considered, says Leo Buhler, a Swiss transplant surgeon in Geneva. He said he would transplant a genetically engineered pig organ into a patient today,
were the patient situation desperate enough. And there are desperate cases. In fact, thousands of people die each year while waiting on transplant lists.
Donated human organs are scarce, and many that become available don end up helping anyone. That is because a heart or kidney lasts only a matters of hours packed in ice,
so organs can reach any but the closest patients. e want to make organs come off the assembly line,
a dozen per day, says Rothblatt. In 2011 her company paid about $8 million to take over Revivicor,
and she has outlined plans for a facility able to breed 1, 000 pigs a year,
complete with a surgical theater and a helipad so organs can be whisked where they are needed.
The problem with xenotransplantation is that animal organs set off a ferocious immune response. Even powerful drugs to block the immune attack can entirely stop it.
The human body reacts even more strongly to pig tissue since pigs are genetically more distant. All human tests of pig organs have ended quickly, and badly.
A Los angeles woman who got a pig liver in 1992 died within 34 hours. The last time a doctor transplanted a pig heart into a person, in India in 1996,
he was arrested for murder. Researchers continue to work with pigs because theye in ready supply,
and the organs of young pigs are about the right size. In order to beat the rejection problem,
researchers began trying to genetically modify the animals. One major step came in 2003 when David Ayares
a cofounder of Revivicor, created pigs whose organs lacked a sugar molecule that normally lines their blood vessels.
That molecule was the major culprit behind what called hyperacute rejection, which had destroyed almost instantaneously transplanted pig organs.
Removing the sugar molecule helped. But it wasn enough. Tests in monkeys showed that other forms of organ rejection still damaged the pig tissue,
albeit more slowly. To combat these effects, Ayares team has made pigs with more and more human genes.
For instance, one gene that been added produces the human version of thrombomodulin, a molecule that prevents clotting in blood vessels.
Although pigs have their own version of thrombomodulin it the wrong shape and doesn work correctly with human blood. e are adding the human genes to the pig
so you have the organ repressing the immune response, rather than have to give a whopping dose of immune suppressants,
says Ayares. By next year, some of the pigs will have as many as eight added human genes.
These genetic changes make their organs more compatible with a human body, but the animals still look
and act like normal pigs. Genetically engineering the pigs isn easy. It challenging to insert human genes
and difficult to get them to function correctly. ou try to put all your genes into one parcel so they go to one place in the genome,
says Bruno Reichart, a professor at the University of Munich, who leads a German consortium developing transgenic pigs. t very cumbersome.
Creating a good pig is really like winning the lottery. n the United states, leading transplant surgeons have been meeting with Revivicor ever few months to plan what genes they like to see added next.
Since last year, some of the genetic engineering has been carried out in collaboration with Synthetic Genomics, a California company started by DNA sequencing entrepreneur J. Craig Venter.
Rothblatt invested $50 million in Venter company in 2014, and it has begun designing and building genetic add-ons
and inserting them into pig cells. It is left to Revivicor to produce piglets from these engineered cells
using cloning. Some people involved in the project are more circumspect than Rothblatt about how fast it can succeed. very time you relieve one rejection issue,
another one comes in behind. You peel back one layer and there is another layer underneath,
who runs the mammalian synthetic biology program for Synthetic Genomics. o one is so naïve as to think, h,
or 100 iterations. et surgeons credit the genetically enhanced pigs with some recent successes. Muhammad Mohiuddin,
a transplant surgeon and researcher at the National Heart, Lung, and Blood Institute, in Bethesda, Maryland, says a heart from one of Revivicor pigs lasted two and a half years inside a baboon.
This milestone, reached last month, surpassed a previous record of 179 days, achieved by Massachusetts General Hospital.
Also this summer, transplant experts at the University of Pittsburgh said they kept a baboon alive with one of Revivicor pig kidneys for more than four months.
That set a record for the longest ife-sustainingxenotransplant between a pig and a primate.
The heart transplants were not life-sustaining but eterotopic? the pig heart was attached to the baboon circulatory system
and was able to beat, but it didn have to do the work of pumping blood,
since the baboon own heart remained in place. Mohiuddin says the pig heart gave out only when he decided to stop giving the baboon the novel immune-blocking drugs he had used. e believe it could have gone on forever,
he says. would say 60 percent of the improvement was due to the organ, and 40 percent due to better drugs. eichart calls the survival of these pig hearts major breakthrough.
He says t gives us all hope that cardiac xenotransplantation works. These hearts remained normalt amazing.
However, he doesn think anyone should be forecasting when a transplant into humans could occur.
That is because surgeons still need to completely replace a baboon heart with one from these pigs
and show it keeps the animal alive. t wouldn be serious to give a time line for use in humans,
he says. Mohiuddin says hel soon begin trying to replace baboon hearts entirely. The organs he used before had three genetic alterations,
but the next ones will have seven. f they survive, then we can consider clinical trials, he says.
Lung transplants will be harder, since lungs are permeated with blood vessels and heavily exposed to the immune system.
So far, transplants last only a matter of days, says Rothblatt. She has been financing research at the University of Maryland,
where pig lungs are being perfused with human blood in the laboratory as a way of measuring the immune response. he wants genetically modified lungs for personal reasons,
due to personal grief, says Reichart. think that is a great thing, but lungs are very difficult. ransplant surgeons say one of the largest obstacles they face is the immense cost of carrying out xenotransplant experiments.
A single transplant surgery costs $100, 000 and involves eight people. Then there the cost of keeping the primates, the red tape of animal regulations,
and limited government grants. That where Rothblatt personal interest and her fortune have made a difference,
says Mohiuddin. he has the money and a personal attachment. She wants to get it done fast. e
#Synthetic Life Seeks Work In the May 15, 2014, edition of the journal Nature, Floyd Romesberg chemistry lab at San diego Scripps Research Institute published a paper titled Semisynthetic Organism with an Expanded Genetic Alphabet.
Romesberg and his colleagues had created a bacterium incorporating chemical building blocks that, as far as anybody knows,
Genome pioneer Craig Venter led a team that manufactured a genome for a germ that causes pneumonia in cows,
Romesberg lab could claim to have made the first living thing with an expanded genetic code. eople would ask what the big deal is said,
except to say it is ell studiedand that they added a new function to it,
a way for another drug to attach to the protein at a specific site. The technology might also pave the way to new biotech drugs.
Nearly all such drugs proteins like insulin or the blood cell-booster erythropoietin, are made inside a bacterium or other cell.
But synthetic DNA could vastly expand what drugs are possible. That is because a normal cell builds proteins from just 20 amino acids,
too big, says Peter Schultz, a Scripps biologist. Romesberg trained in Schultz lab.)Eventually, there could be bacteria producing entirely new proteins. o make a billion-dollar business, yes,
we need a protein, says Romesberg. he home run is the ability to produce therapeutic proteins with unnatural amino acids in them. ynthorx achievement falls a bit short of that.
It made its first protein by breaking up its E coli and using their unnatural genes to make a novel protein molecule in a test tube reaction.
including new vaccines. It might be possible, for instance, to make a tuberculosis virus with unnatural DNA in it.
It would be a real, living virus. But without any raw material to copy its genes (that is,
but also benign, that would be the perfect vaccine, says Schultz. Synthetic life forms have implications far beyond new products.
Steven Benner, a synthetic biologist and a founder of the Foundation for Applied Molecular Evolution in Gainesville, Florida, asks.
Benner, who works with NASA trying to find life on other planets, suggests that synthetic biology might also improve the ability to detect new earthly life forms. aybe they exist on earth,
but we just don know what to look for, he says. t forces you to ask unscripted questions to challenge your fundamental core hypotheses. ynthorx isn the only startup looking to expand upon the life code for commercial reasons.
Harvard university scientist George Church and his former student, Farren Isaacs, of Yale, held a press conference to announce a breakthrough of their own.
Both Romesberg and Church reported a tiny fraction of the bacteria managed to slip the genetic handcuffs via mutation.
an artificial organism might somehow scavenge up a substitute chemical from the environment to replace the critical one fed to it in the labs
Schultz thinks there will be medical uses of synthetic organisms long before they are released into the environment to eat oil
And once synthetic biology leads to a new drug or vaccine, he thinks, wel get used to the idea of inventing life for our own good. ne has to pick the most near-term applications of this technology to show what it can really do for the good of mankind,
Schultz says. think medicine is one area of pretty obvious applications. d
#Transplant Surgeons Revive Hearts After Death Transplant surgeons have started using a device that allows them to eanimatehearts from people who have died recently,
and use the organs to save others. The eart in a boxis a wheeled cart with an oxygen supply, a sterile chamber,
Doctors say it may extend the time a heart can last outside the body and is letting them recover hearts from donors who haven been eligible before.
In at least 15 cases, surgeons in the United kingdom and Australia say they have used the system to successfully transplant hearts removed from patients after theye died.
heart transplants only come from brain dead donors whose hearts are cut away while their bodies are still healthy.
and 30 percent, say doctors, saving the lives of people who would otherwise die from heart failure.
In the U s. about 2, 400 heart transplant occur each year, a figure that has remained essentially unchanged for 20 years.
surgeons at St vincent Hospital in New south wales described three cases in which they waited as little as two minutes after a person heart stopped before they began removing it.
where it began beating again after being fed with oxygenated blood and electrolytes. Without such help, surgeons consider hearts from dead donors too damaged to use. he device is vital.
The heart gets an absolutely essential infusion of blood to restore its energy, says Stephen Large, a surgeon at Papworth Hospital in the United kingdom,
which has used the system as part of eight heart transplants. Transplant surgeons recognize two major categories of death.
People can be brain dead, or they die because the heart and blood flow stop. The latter is
what they now call irculatory death. But by the time it stops on its own, a person heart is starved of oxygen
and the muscle cells are already dying. Left at body temperature, the damage, called ischemia, progresses rapidly.
In recent tests of such techniques, called warm perfusion, scientists have shown they can cut off a pig leg then replace it 12 hours later
a transplant surgeon at the Massachusetts General Hospital. arm is the way to go with metabolically active tissue.
The first successful heart transplant, in 1967, was carried out in South africa from a 25-year-old car accident victim
But surgeons found that hearts that stop naturally often didn start again, or can pump blood,
says Large, the Papworth surgeon. The crisis is particularly severe in the U k, . where handguns and some other firearms are prohibited,
unlike in the U s. There are more than twice as many heart donors per capita in the U s as in the U k. Large believes taking hearts from circulatory-death donors could expand the supply in the U k. by almost a third,
Donors at the Papworth hospital have included victims of car accidents and failed suicide attempts by hanging.
They had severe brain damage but were not brain dead. These patients are usually on mechanical ventilators and some,
though not all, die shortly after their family chooses to remove life support. If their hearts do stop,
the ethical dilemma is how long surgeons should wait before swooping in to retrieve organs. In the U s.,the accepted standard is five minutes,
although Colorado surgeons in 2008 took hearts from brain-damaged newborns after waiting only 75 seconds.
Robert Truog, a medical ethicist at Harvard university, says a question is whether these donors are given really dead
Large hospital, in a rural area a half hour drive from Cambridge, has taken some new and even more radical steps,
All eight transplants so far have been successful he says. One patient was identified publicly as Huseyin Ulucan, a 60-year-old from London w
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