#Scientists use 3-D printer to speed human embryonic stem cell research A blog by Scientific American.
Depositing human embryonic stem cells in cultures using a 3-D printer offers some advantages.
Whereas human embryonic stem cells have proved too fragile to print in the past, scientists at Scotland s Heriot-Watt University and Roslin Cellab
or a polymer that hardens#either naturally or after being sintered by a laser#into a particular structure.
So-called"bioprinters naturally use cells rather than plastics to create organic structures. However this technique can damage the printed cells,
so the Heriot-Watt and Roslin Cellab scientists developed a printing system driven by pneumatic pressure and controlled by the opening and closing of a microvalve.
any tissue formed would yield better models of human biology than those formed from mouse cells.
that challenged the legality of funding for the work by the National institutes of health (NIH. This means NIH-funded researchers can continue to work with the 195 new human embryonic stem cell lines the federal government has made available to them.
Researchers at the University of Pennsylvania s Tissue Microfabrication Laboratory, the Wake Forest Institute for Regenerative medicine and elsewhere are developing methods for bioengineering functional vessels that could someday be used to ferry blood around 3-D-printed organs.
A more immediate benefit of 3-D printing embryonic stem cells might be the ability to make tissue samples that could be used to accurately test drug compounds for toxicity in humans, without the need for animal testing, according to the researchers c
#Taking the crystals out of X-ray crystallography The technique that revealed DNA's double helix
and the shapes of thousands of other molecules is getting an upgrade. A method described in Nature this week1 makes X-ray crystallography of small molecules simpler, faster and more sensitive,
largely doing away with the laborious task of coaxing molecules to form crystals. Instead, porous scaffolding holds molecules in the orderly arrangement needed to discern their structure with X-rays.
You could call it crystal-free crystallography, says Jon Clardy, a biological chemist at Harvard Medical school in Boston,
Massachusetts, who was involved not in the work but wrote a commentary accompanying the paper2. X-ray crystallography is one of the most important techniques in science,
because it is one of only a few ways to directly determine the shape of large molecules.
It does this by blasting molecules with X-rays and measuring how their rays are diffracted. Transforming these reflections into molecular models isn t simple.
But cajoling many molecules to crystallize is tedious and time-consuming#like getting a puppy to sit still for a photograph#and,
Clardy says, the biggest bottleneck in X-ray crystallography.""Some crystallize easily, some crystallize hardly and some are impossible to crystallize,
a chemist at the University of Tokyo who led the work along with colleague Yasuhide Inokuma.
Ewen Callaway interviews biological chemist Jon Clardy about the significance of the new technique for deciphering molecular structures.
"Our next grand challenge is to apply this method to protein crystallography, he says
#Synthetic vaccine could prevent future outbreaks of foot-and-mouth disease Virologists have devised a way to create an entirely synthetic vaccine for foot-and-mouth disease.
The vaccine could prevent future outbreaks of the disease, and potentially lead to new treatments for polio and other human diseases.
Bryan Charleston, head of the Livestock Viral Diseases Programme at the Pirbright Institute in Woking, UK,
and his colleagues used computer simulations to create a model of the protein shell of the virus that causes the disease,
then reconstructed it from synthetic protein components. The synthetic shell contains no genetic material and so it cannot infect the animals.
But it will spur the immune system to produce antibodies that would protect them from the real virus. In 2001,
an outbreak of foot-and-mouth disease in the United kingdom led to the destruction of nearly 10 million animals.
It cost the economy an estimated#8. 5 billion (US$12. 9 billion) in agricultural and tourism costs,
and spurred a decision to protect against future outbreaks with vaccination rather than mass slaughter.
In 2007, however a vaccine made from inactivated virus caused another UK outbreak. The authors say that there is absolutely no chance that their new vaccine could revert into an infectious virus
because it contains no viral genes. Also being entirely synthetic, it cannot be contaminated with live virus during manufacturing.
It will be 6-8 years before the vaccine is available to farmers, they estimate. But if the method used to create the vaccine proves successful when scaled to commercial production,
it could also be used to create vaccines for human diseases that are caused by viruses of the same family, such as hand, foot and mouth disease,
which is ubiquitous in Southeast asia, and polio, which still blights the lives of millions of people in the developing world."
"Viruses are all very different from each other, and each will come with its own set of problems to solve,
says co-author David Stuart, a structural biologist at the University of Oxford, UK, who is working with the World health organization
and the Gates Foundation to apply the techniques to the eradication of polio. But if we could use this to move away from inactivated polio viruses in the vaccines,
it would have very powerful impacts because we are so close to ending this disease. JEFF J MITCHELL/REUTERSA 2001 outbreak of foot and mouth disease led to the slaughter of huge numbers of sheep and cows.
Earlier attempts to produce a synthetic vaccine for foot and mouth disease were thwarted often by peculiarities of viral geometry.
Both the polio and foot-and-mouth viruses are shaped as an icosahedron#a polyhedron with 20 triangular faces."
"When those are clipped together, it s the edges that are the weak spots, explains Charleston. The synthetic protein shells simply fall apart during transport
and dissemination, rendering the product useless. The team got around the problem by engineering the vaccine to have disulphide bonds cross-linking the protein triangles together.
This makes the structure more stable, which means it will not require cold storage and that it will be cheaper to produce
says John Oxford, a virologist at St bartholomew s and the Royal London Hospital.""This really is an ace paper#they've truly given the entire issue a whole new dimension,
and Charleston that the new vaccine is unable to cause an infection or outbreak. Marvin Grubman, an animal-disease researcher at the US Department of agriculture in Orient Point, New york, says that the new vaccine"is a good piece of work,
but certainly not very novel, pointing to a foot-and-mouth vaccine his team devised that uses adenovirus to deliver empty viral shells.
That vaccine, he says, has been approved for use in the United states for cases of emergency. The authors however point out that their vaccine does not require the injection of live viruses
and that it would be suitable for preventive vaccination as well as in cases of severe outbreaks o
#Scientists map protein that creates antibiotic resistance Japanese researchers have determined the detailed molecular structure of a protein that rids cells of toxins,
but can also reduce the effectiveness of some antibiotics and cancer drugs by kicking them out of the cells they are targeting.
one of a class known as multidrug and toxic compound extrusion transporters (MATES) that are found in cell membranes.
The discovery suggests new approaches to combat antibiotic resistance and boost the power of cancer therapies,
partly because researchers had a poor understanding of how these proteins work. But in the past three years scientists have made some progress mapping the transporters detailed architecture.
A team led by biophysicist#Osamu Nureki, of the University of Tokyo, #reports that the membrane-bound protein is shaped like A'v',
says Hendrik Van veen, a pharmacologist at the University of Cambridge, UK.""They have a direct mechanism of how the protons change the shape of the cavity.
Geoffrey Chang, a structural biologist at the University of California, San diego, says that the findings are very similar to those for the MATE protein from Vibrio cholerae, the bacterium that causes cholera.
These results represent refinements of numbers obtained by previous missions such as the Wilkinson Microwave Anisotropy Probe (WMAP.
breaks the most new ground is in its support for the reigning theory that describes the instant after the Big bang. The theory, known as inflation,
"Planck could have found that there was something majorly wrong with inflation, says astrophysicist Jo Dunkley at the University of Oxford, UK,
who has worked on data from Planck and the WMAP.""Instead, we ve got new evidence that this expansion did happen.
In the minutes that followed the burst of inflation, particles such as protons and electrons formed from the cauldron of proto-matter,
and photons began to bounce around like pinballs. It was only 380,000#years later, when the charged plasma cooled into neutral atoms,
that those photons could fly freely. Today they make up the CMB, and carry with them an imprint of the quantum fluctuations that roiled the inflationary Universe.
says Paul Shellard, a Planck cosmologist at the University of Cambridge, UK. SLIDESHOW: Homing in on the cosmic microwave background In 1965,
Their giant but crude microwave receiver saw the radiation as being the same in all directions,
NASATHE Wilkinson Microwave Anisotropy Probe, launched in 2001, improved on COBE by looking for such anisotropy at much smaller angular scales.
But unambiguous confirmation of a cosmic burst of expansion known as inflation remains elusive. ES a
But for those who argue that investments in basic research are necessary for innovation and prosperity,"this is a really bad budget,
says James Turk, executive director of the Canadian Association of University Teachers in Ottawa, Ontario.""There is a consistent pattern of steering money away from basic research,
says Turk.""More and more of it is being directed to company needs. No one expected major spending increases in this budget,
as the Conservative government of Prime minister Stephen Harper tries to eliminate the deficit by 2015 amid a dreary economic outlook.
It includes a Can$225 million (US$225 million) boost for research infrastructure at universities through the Canada Foundation for Innovation.
That money comes from interest accrued on the foundation s endowment that the government is now releasing for use
but that money is earmarked for research partnerships with industry rather than basic research. The National Research Council,
But this year, the government offered some support for clean energy companies. Sustainable development Technology Canada, a foundation that supports clean technology startup companies, will get Can$325 million over 8 years.
This investment was welcomed by Clare Demerse, federal policy director at the Pembina Institute, an energy policy think tank in Calgary.
Although the money is less than half the investment that Pembina and others had called for, Demerse said in a statement that it would be a"lifeline for the country s estimated 700 clean technology companies.
But the government s relentless focus on business innovation does not represent a coherent science strategy,
says Paul Dufour, director of Paulicy Works, a science-and-technology consultancy in Gatineau, Quebec.
He notes that the budget makes no reference to a national science -and-technology strategy that Harper released in 2007."
there is a piecemeal approach, with the government"picking winners and providing new money to the automotive, aerospace, forestry and aquaculture sectors."
"For cosmologists, this map is a gold mine of information, says George Efstathiou, director of the Kavli Institute for Cosmology at the University of Cambridge, UK,
and one of Planck s lead researchers. The results strongly support the idea that in the 10##32 seconds or so after the Big bang,
the Universe expanded at a staggering rate#a process dubbed inflation. Inflation would explain why the Universe is so big,
and why we cannot detect any curvature in the fabric of space (other than the tiny indentations caused by massive objects such as black holes).
and neutral atoms of hydrogen and helium were beginning to form from the seething mass of charged plasma.
in a pattern that carried the echoes of inflation. Those photons are still out there today
as a dim glow of microwaves with a temperature of just 2. 7 kelvin. Since the cosmic microwave background was detected first in 1964,
two space-based experiments#the Cosmic Background Explorer (COBE) and the Wilkinson Microwave Anisotropy Probe (WMAP)# have mapped the tiny temperature variations within it.
Those data have enabled cosmologists to work out when the Big bang happened, estimate the amount of unseen dark matter in the cosmos
Its high-frequency microwave detector is cooled to just 0. 1 degrees above absolute zero which enables it to detect temperature variations as small as a millionth of a degree.
These precise measurements show that the Universe is expanding slightly slower than estimated from WMAP's data.
The Planck data also implies that dark energy makes up 68.3%of the energy density of the Universe,
a slightly smaller proportion than estimated from WMAP data. The contribution of dark matter swells from 22.7%to 26.8%
The simplest models of inflation predict that fluctuations in the cosmic microwave background should look the same all over the sky.
This rules out some models of inflation, but does not undermine the idea itself, he adds.
however, raise tantalizing hints that there may yet be new physics to be discovered in Planck s data.
So far, the team has analysed about 15.5 months of data, and"we have about as much again to look at,
The team expects to release the next tranche of data in early 2014 a
#Serotonin receptors offer clues to new antidepressants Researchers have deciphered the molecular structures of two of the brain's crucial lock-and-key mechanisms.
appetite and mood#and could provide targets for future drugs to combat depression, migraines or obesity.#"
says Bryan Roth, a neuropharmacologist at the University of North carolina Chapel hill Medical school, and a co-author of the two studies published in Science today1,
2."Before this there was no crystal structure for any serotonin receptor. A lot of what was theoretical is known now with a great degree of certainty,
Roth and his colleagues uncovered the receptor structures using X-ray crystallography in which X-ray beams are fired at crystals of the compound,
and the structure is deduced from how the beams scatter. The teams focused on two receptors, called 1b and 2b.
Although the difference was a mere 0. 3 nanometres, about the width of three helium atoms,
Roth says that learning to control the cascades is likely to be crucial in maximizing beneficial effects of drugs
and represent the latest success for a'fringe'therapy in which a type of immune cell called T cells are extracted from a patient, genetically modified,
says Michel Sadelain, a researcher at the Memorial Sloan-Kettering Cancer Center in New york and an author of the study.
whether it could take on the faster-growing acute lymphoblastic leukaemia, a tenacious disease that kills more than 60%of those afflicted.#
#Carl June, an immunologist at the University of Pennsylvania in Philadelphia and a pioneer in engineering T cells to fight cancer, says that he is surprised that the method worked so well against such a swift-growing cancer.
is to move the technique out of the boutique academic cancer centres that developed it and into multicentre clinical trials."
"What needs to be done is to convince oncologists and cancer biologists that this new kind of immunotherapy can work,
he says. Oncologist Renier Brentjens, also at Memorial Sloan-Kettering Cancer Center, remembers the day that he had to tell one of the patients in the trial that the weeks of high-dose chemotherapy the 58-year-old man had endured had worked not after all."
"It was painful to have that conversation, says Brentjens.""He tells me now it was the worst news he has heard ever in his life.
Another month in the hospital on intensive chemotherapy drugs did nothing to help. By the time the man started the trial,
and engineered them to express a chimeric antigen receptor, or CAR, that would target cells expressing a protein called CD19.
Because CD19 is found on both healthy and cancerous B cells, the engineered T cells were unable to discriminate between the two.
The treatment had driven his cancer into remission#as it did for the other four patients in the trial
#so he became eligible for a bone-marrow transplant. A hundred days later, he is doing well,
Four of the five patients were well enough to receive transplants; the remaining patient relapsed and was ineligible.
Pharmaceutical firms have tended to be wary of the CAR technique because it is technically challenging,
and faces an untested path to regulatory approval, says Steven Rosenberg, head of the tumour immunology section at the National Cancer Institute in Bethesda, Maryland.
as well as the launch of several SMALL CAR-focused biotechnology firms. And Sadelein says that he is an investigator on a trial with the Dana-Farber Cancer Institute in Boston
Massachusetts, to test whether the technique can be exported to other treatment centers, among other outcomes.
#'Hologram-lite'idea for 3d phone displays Now physicist David Fattal and his colleagues at Hewlett-packard Laboratories in Palo alto have developed a sort of'hologram-lite'approach.
Light from light-emitting diodes is sent then sideways through the slab, and some of it is scattered out of the slab in a direction determined by the spacing and orientation of the grooves.
the display beams different images in different directions, so that a person's left and right eyes see slightly different images#a requirement for the brain to process an image as 3d.
Moving the display screen around also produces different images, so that it appears as if the object were being viewed from up to 64 different vantage points over a field of view spanning 90 degrees.
as in an ordinary LCD screen#the display can also produce moving images. Figuring out how to modulate the LCD screen to produce the views is orders of magnitude easier than working out the complicated interference patterns needed to make a moving hologram visible from any direction,
says Fattal. And because each circular diffraction grating is just 12 micrometres across, the system is suited ideally to mobile technologies,
Existing 3d-display technologies tend to have larger pixel sizes and therefore operate better at distances of a few metres,
For example, many commercial 3d televisions use lenses to send underlying light sources in different directions. But the pixels in that case tend to be larger
he explains, because it is difficult to produce small lenses of high optical quality. Nick Holliman, a computer scientist at Durham University, UK, describes the work from Fattal's team as a very nice idea and a great technology demonstrator.
But he points out that light designed to bleed between each of the 64 different views#to prevent jarring jumps#is 10 times as bright as typically used.
#Waterproof transistor takes cell's electric pulse Think of it as a medical monitor for the cell.
The device is known as a single-electron transistor, and its inventors hope that it could be used to measure the performance of biofuel-producing organisms,
A transistor acts like a switch in an electrical circuit: a voltage at the transistor s gate terminal allows current to flow through a semiconductor inside the device.
If the semiconductor is small enough#a nanoparticle, for example#a single electron can switch the transistor on,
amplifying a tiny signal into a much larger current in the main circuit. The first single-electron transistors were built in the late 1980s1,
but most require very low temperatures#otherwise, the electrons gather enough energy to tunnel through the semiconductor,
and current leaks through the switch. A handful work at room temperature (by using carbon nanotubes to detect electrons
for example2), but they cannot operate in water#a serious obstacle to using such devices in living organisms.
In 2008, materials scientist Ravi Saraf at the University of Nebraska-Lincoln and his colleagues built a room-temperature single-electron transistor using a different approach3.
They strung together thousands of gold nanoparticles, each 10 nanometres across, into long necklaces. These can form a tangled network that connects two electrodes some 30 micrometres apart.
Roughly 5%of the gold nanoparticles have defects that prevent current from flowing from one electrode to the other.
But if an electron settles on a defective nanoparticle it makes it slightly easier for current to flow,
and the transistor switches on.""Saraf takes advantage of the fact that these one-dimensional arrays are not perfect,
says Ulrich Simon, a nanoscience researcher at the RWTH Aachen University in Germany. Now, Saraf s team has shown that the nano-necklace device works in water
and can monitor a cell s vital signs.""That s something really new, says Simon. The cells sit on the surface of the gold#nano particles,
where subtle changes in the charge distribution across the cell membrane can bridge the defects and switch the transistor on.
Their results are due to appear in Advanced Materials. The device can fit about five green algae cells between the electrodes.
Shining a light on the cells triggers a cascade of biochemical reactions that transfer electrons along a chain of molecules#and switches the transistor on.
Adding more carbon dioxide, or using wavelengths of light that are absorbed easily by chlorophyll, increases the rate of photosynthesis and produces a larger current through the transistor.
Other researchers are trying to repurpose the biochemistry of green algae to make biofuels, and Saraf thinks that his device could monitor how efficiently the new strains photosynthesize.
He also hopes to test the effects of candidate drugs on the metabolism of human cells, by monitoring ph changes, for example."
"Now that we can do this in water, we want to try mammalian cells, Saraf says
#Gene-analysis firms reach for the cloud For Chaim Jalas at the Center for Rare Jewish Genetic disorders in New york,
DNA sequencing is the easy part. It costs less than US$1, 500 per person to have the important parts of his clients genomes sequenced.
But it would be dauntingly expensive to maintain servers and staff to analyse the data
and identify mutations that might be causing the undiagnosed diseases that afflict his clients families.
So Jalas, the centre s director of genetics resources and services, has outsourced parts of the analysis. He uploads his clients sequencing data to cloud-computing software platforms
where he can run analyses without having to set up the infrastructure in-house. The cost is about $100 per person.
And the cloud-based interfaces let him collaborate with doctors in Israel without worrying about repeatedly transferring data on slow Internet connections."
"For me, it is convenient and cost-efficient, he says. Jalas and the way he works represent a new and mostly untapped market for a new crop of genetics interpretation and analysis firms,
which will be touting for customers at a meeting of the American College of Medical Genetics and Genomics in Phoenix, Arizona, on 19-23 march.
Dozens of these firms have emerged, some in the past year, as ever more affordable sequencing moves from academia into the clinic (see Nature 494,290-291;
2013). ) Doctors will increasingly want to use sequen#cing data to guide decisions about patient care,
but might not necessarily want to invest in staff and software to make sense of those data."
"It s a huge unmet need, says David Ferreiro, a biotechnology analyst with investment bank Oppenheimer & Company in New york,
which invests in many sequencing-technology and-analysis companies. Where there is a need, there is also money to be made.
The companies, many of them based in California s Silicon valley, have been tempted by a market in outsourced sequencing
and analysis software that by 2016 could top $4#billion per year, according to BCC Research, a market-research company in Wellesley,
Massachusetts (see Genes in the marketplace).""The sky s the limit, says Andreas Sundquist, chief executive of DNANEXUS in Mountain view, California,
which provides genetic analysis software on its cloud-based platform and allows users to upload and run their own algorithms.
Source: BCC Researchother firms offer a range of approaches. Seven Bridges Genomics, based in Cambridge, Massachusetts,
aims to be accessible to people with no expertise in bioinformatics, and provides access to free tools for designing custom-made analysis pipelines.
Ingenuity Systems in Redwood City, California, allows users to upload a list of mutations in a person s genome,
and finds those most likely to cause disease. Personalis, down the road in Menlo Park, offers sequencing services and interpretation for clinicians and pharmaceutical and biotechnology companies.
Last week, the company won a $1. 53-million contract with the US Department of veterans affairs to look for genetic variants in samples from as many as one million military veterans
to explore the variants roles in disease. The company will outsource the sequencing to Illumina,
a market leader in sequencing technology based in San diego, California.)The activity is reminiscent of that a decade ago,
when bioinformaticians started up a flurry of companies, most of which were unsuccessful because the path from a genetic-disease marker to a profitable drug has not been straight#forward.
Today s companies have moved on to other challenges, says Steven Brenner, a computational genomicist at the University of California, Berkeley.
He says that they will have to prove that their products are better than freely available software
#and do so without disclosing their intellectual property.""These companies have a tricky situation, he says.
And they are facing competition from the sequencing-technology firms themselves. Last year, Illumina opened Basespace Apps, a marketplace for online analysis tools to be used on data uploaded to the company s own cloud-computing platform.
Information-technology companies are getting in on the action, too: Oracle, based in Redwood Shores, California, has its own products aimed at helping researchers
and hospitals to analyse data. But one of the biggest questions will be how deeply analysis companies can reach into medical settings,
where privacy concerns are paramount. Hospitals can be fined if patient privacy is compromised, and clinical geneticists may be uneasy about uploading data to the cloud."
"It s your licence and your lab that go on the line when it comes to reporting a clinical result,
says Elizabeth Worthey, director of genomic informatics at the Human and Molecular genetics Center at the Medical College of Wisconsin in Milwaukee.
That is a large part of why many hospitals have chosen so far to build their own analysis infrastructure,
says Ferreiro. To address privacy concerns, Bina Technologies in Redwood City sells a server that can sit in a customer s own data centre
and is optimized to run genome-analysis software. Knome of Cambridge Massachusetts, announced last year that it plans to sell $125, 000 genome-analysis machines for use in customers labs (see Nature 490,157;
2012). ) It seems unlikely that any single analysis company will rule the market; the range of customers who need to interpret sequence data is growing,
and each has their own needs.""We would rather see a thousand flowers bloom, says Sundquist."
"I don t think we re going to see consolidation anytime soon
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