#A natural light switch MIT scientists, working with colleagues in Spain, have discovered and mapped a light-sensing protein that uses Vitamin b12 to perform key functions,
including gene regulation. The result, derived from studying proteins from the bacterium Thermus thermophilus, involves at least two findings of broad interest.
First, it expands our knowledge of the biological role of Vitamin b12, which was understood already to help convert fat into energy,
and to be involved in brain formation, but has now been identified as a key part of photoreceptor proteins the structures that allow organisms to sense
and made it a light sensor, says Catherine Drennan, a professor of chemistry and biology at MIT.
The findings are detailed this week in the journal Nature. The paper describes the photoreceptors in three different states:
to understand how it works at each stage, Drennan says. The paper has nine co-authors,
graduate students Percival Yang-Ting Chen, Marco Jost, and Gyunghoon Kang of MIT; Jesus Fernandez-Zapata and S. Padmanabhan of the Institute of Physical chemistry Rocasolano, in Madrid;
and Maria Carmen Polanco, of the University of Murcia, in Murcia, Spain. The researchers used a combination of X-ray crystallography techniques
and in-vitro analysis to study the bacteria. Drennan, who has studied enzymes that employ Vitamin b12
since she was a graduate student, emphasizes that key elements of the research were performed by all the co-authors.
Jost performed crystallography to establish the shapes of the structures, while the Spanish researchers, Drennan notes, id all of the control experiments to show that we were really thinking about this right,
of which exactly three are bound to the genetic material something Drennan says surprised her. hat the best part about science,
says Rowena Matthews, a professor emerita of biological chemistry at the University of Michigan, who has read the paper.
#Researchers disguise drugs as platelets to target cancer Researchers have developed for the first time a technique that coats anticancer drugs in membranes made from a patient own platelets,
and attack both primary cancer tumors and the circulating tumor cells that can cause a cancer to metastasize.
The work was tested successfully in an animal model. here are two key advantages to using platelet membranes to coat anticancer drugs,
says Zhen Gu, corresponding author of a paper on the work and an assistant professor in the joint biomedical engineering program at North carolina State university and the University of North carolina at Chapel hill. irst,
not only attack the main tumor site, but are more likely to find and attach themselves to tumor cells circulating in the bloodstream essentially attacking new tumors before they start,
says Quanyin Hu, lead author of the paper and a Ph d. student in the joint biomedical engineering program.
Here how the process works. Blood is taken from a patient a lab mouse in the case of this research
and the platelets are collected from that blood The isolated platelets are treated to extract the platelet membranes,
which are placed then in a solution with a nanoscale gel containing the anticancer drug doxorubicin (Dox),
and creating nanoscale spheres made up of platelet membranes with Dox-gel cores. These spheres are treated then
these pseudo-platelets can circulate for up to 30 hours as compared to approximately six hours for the nanoscale vehicles without the coating.
When one of the pseudo-platelets comes into contact with a tumor, three things happen more or less at the same time.
Third, the nanoscale pseudo-platelet is swallowed effectively by the larger cancer cell. The acidic environment inside the cancer cell then begins to break apart the pseudo-platelet freeing the Dox to attack the cancer cell nucleus. In a study using mice,
the researchers found that using Dox and TRAIL in the pseudo-platelet drug delivery system was significantly more effective against large tumors
and circulating tumor cells than using Dox and TRAIL in a nanogel delivery system without the platelet membrane. e like to do additional preclinical testing on this technique,
Gu says. nd we think it could be used to deliver other drugs, such as those targeting cardiovascular disease, in
which the platelet membrane could help us target relevant sites in the body
#Raising Computers to Be Good Scientists Making sense of the new scientific data published every year including well over a million cancer-related journal articles is a tall order for the contemporary scientist.
Even if a scientist were capable of reading every article and memorizing its content, drawing connections to answer real-world questions would require supernatural cognition.
Figuring out how to actually read hundreds of thousands of scientific papers and apply their findings to real challenges,
such as the treatment of cancer patients, is an arduous, uphill battle. But an associate professor in the University of Arizona School of Information
Clayton Morrison, is doing just that one algorithm at a time. He wonders, as many others in his field do,
if the solutions to big problems are already there, in extant data, but no one has been able to put it all together yet.
Morrison, as the co-principal investigator, and a team of collaborators are using a research grant of more than $3. 6 million to investigate.
Funded by the Defense Advanced Research Projects Agency, EACH: Reading and Assembling Contextual and Holistic Mechanisms From Textwill create a computer system that reads papers, extracts information on biochemical pathways,
and plugs it all into large-scale, interactive models. REACH researchers are laying the foundation for interactive software that would allow drug developers,
or maybe even doctors, to provide lots of information, such as a patient genome. In turn, it could model how a specific treatment would interact with the patient. heyl be the Microsofts and Googles of biomedicine,
Morrison said. Its potential has mass appeal and big implications: fast, individualized and precise biomedical care. he REACH project is applied to cancer biology,
but we have an even bigger vision than that, although cancer biology is big enough,
Morrison said. If big data is a two-part challenge, Morrison said, then storing it and moving it around is the first part.
The second part is understanding it. REACH works on the understanding part in three phases:
extraction, assembly and inference. Extraction was put to the test this summer. Over the course of a year, researchers led by Mihai Surdeanu,
associate professor in the School of Information and REACH principal investigator, trained a computer system to read papers using hundreds of algorithms.
One, for example, allows it to understand that ouse, iceand us musculusall refer to the same thing.
Others on the UA research team include Ryan Gutenkunst, assistant professor of molecular and cellular biology; Guang Yao, assistant professor of molecular and cellular biology;
and Kobus Barnard, professor of computer science. Morrison, who also has a strong, academic background in developmental psychology, said,
think that collaborative computers are going to be like children, and wel have to raise them, in a way.
Theyl be as smart as wee able to teach them, and we need them to be able to communicate with us.
In the recent evaluation of this first phase of REACH, the system was able to process 1, 000 papers on RAS-related cancers in a matter of hours,
yielding results that exceeded state-of-the-art predecessors all by relying on algorithms. Asking a human scientist to do the same would be outrageous.
Focusing their efforts on modeling how RAS functions in cancer cells was an easy choice, for a couple of reasons.
Secondly, RAS oncogenes are mutated in 33 percent of all human cancers, making them one of the most highly researched classes of oncogenes.
by teaching it to differentiate between species (a yeast cell is different from a mouse).
As of now, REACH is already familiar with 30 different species affected by RAS-related cancers.
much as a scientist or a doctor might. would like to see this usher in computers understanding complex things at a level that we just can,
animals A new test detects virtually any virus that infects people and animals, according to research at Washington University School of medicine in St louis,
Many thousands of viruses are known to cause illness in people and animals, and making a diagnosis can be an exhaustive exercise,
at times requiring a battery of different tests. That because current tests aren sensitive enough to detect low levels of viral bugs
or are limited to detecting only those viruses suspected of being responsible for a patient illness. ith this test,
you don have to know what youe looking for, said the study senior author, Gregory Storch, MD,
the Ruth L. Siteman Professor of Pediatrics. t casts a broad net and can efficiently detect viruses that are present at very low levels.
We think the test will be especially useful in situations where a diagnosis remains elusive after standard testing or in situations in
which the cause of a disease outbreak is unknown. Results published online in September in the journal Genome Research demonstrate that in patient samples the new test called Virocap can detect viruses not found by standard testing based on genome sequencing.
The test could be used to detect outbreaks of deadly viruses such as Ebola Marburg and severe acute respiratory syndrome (SARS),
as well as more routine viruses, including rotavirus and norovirus, both of which cause severe gastrointestinal infections. Developed in collaboration with the university Mcdonnell Genome Institute,
the test sequences and detects viruses in patient samples and is just as sensitive as the gold-standard polymerase chain reaction (PCR) assays,
which are used widely in clinical laboratories. However, even the most expansive PCR assays can only screen for up to about 20 similar viruses at the same time.
The Washington University researchers are making the technology they developed publicly available to scientists and clinicians worldwide
for the benefit of patients and research. The researchers evaluated the new test in two sets of biological samples for example, from blood, stool and nasal secretions from patients at St louis Children Hospital.
In the first, standard testing that relied on genome sequencing had detected viruses in 10 of 14 patients.
But the new test found viruses in the four children that earlier testing had missed. Standard testing failed to detect common, everyday viruses:
influenza B, a cause of seasonal flu; parechovirus, a mild gastrointestinal and respiratory virus; herpes virus 1, responsible for cold sores in the mouth;
which causes chickenpox. In a second group of children with unexplained fevers, standard testing had detected 11 viruses in the eight children evaluated.
But the new test found another seven, including a respiratory virus called human adenovirus B type 3a,
but can cause severe infections in some patients. In all the number of viruses detected in the two patient groups jumped to 32 from 21,
an instructor of pediatrics. light genetic variations among viruses often can be distinguished by currently available tests
In addition, because the test includes detailed genetic information about various strains of particular viruses, subtypes can be identified easily.
while standard testing identified a virus as influenza A, which causes seasonal flu, the new test indicated that the virus was a particularly harsh subtype called H3n2.
In all the research team included 2 million unique stretches of genetic material from viruses in the test.
their genetic material could easily be added to the test, Storch said. The researchers plan to conduct additional research to validate the accuracy of the test,
so that it could be used to detect pathogens other than viruses, including bacteria, fungi and other microbes,
as well as genes that would indicate the pathogen is resistant to treatment with antibiotics or other drugs, said co-author Kristine Wylie, Phd, assistant professor of pediatrics.
In the meantime, the technology can be used by scientists to study viruses in a research setting. Kristine Wylie investigates the viruses that set up residence in and on the human body, collectively known as the virome.
#Making Batteries with Portabella Mushrooms Can portabella mushrooms stop cell phone batteries from degrading over time?
Researchers at the University of California, Riverside Bourns College of Engineering think so. They have created a new type of lithium-ion battery anode using portabella mushrooms,
which are inexpensive, environmentally friendly and easy to produce. The current industry standard for rechargeable lithium-ion battery anodes is synthetic graphite,
which comes with a high cost of manufacturing because it requires tedious purification and preparation processes that are also harmful to the environment.
With the anticipated increase in batteries needed for electric vehicles and electronics, a cheaper and sustainable source to replace graphite is needed.
Using biomass a biological material from living or recently living organisms, as a replacement for graphite, has drawn recent attention because of its high carbon content, low cost and environmental friendliness.
UC Riverside engineers were drawn to using mushrooms as a form of biomass because past research has established they are highly porous,
meaning they have a lot of small spaces for liquid or air to pass through. That porosity is important for batteries
because it creates more space for the storage and transfer of energy, a critical component to improving battery performance.
In addition, the high potassium salt concentration in mushrooms allows for increased electrolyte-active material over time by activating more pores
gradually increasing its capacity. A conventional anode allows lithium to fully access most of the material during the first few cycles
and capacity fades from electrode damage occurs from that point on. The mushroom carbon anode technology could,
with optimization, replace graphite anodes. It also provides a binderless and current-collector free approach to anode fabrication. ith battery materials like this,
future cell phones may see an increase in run time after many uses, rather than a decrease,
due to apparent activation of blind pores within the carbon architectures as the cell charges and discharges over time,
said Brennan Campbell, a graduate student in the Materials science and engineering program at UC Riverside. The research findings were outlined in a paper, io-Derived, Binderless,
Hierarchically Porous Carbon Anodes for Li-ion Batteries, published on Sept. 29 in the journal Nature Scientific Reports.
It was authored by Cengiz Ozkan and Mihri Ozkan, both professors in the Bourns College of Engineering,
and three of their current or former graduate students: Campbell, Robert Ionescu and Zachary Favors. Nanocarbon architectures derived from biological materials such as mushrooms can be considered a green and sustainable alternative to graphite-based anodes,
said Cengiz Ozkan, a professor of mechanical engineering and materials science and engineering. The nanoribbon-like architectures transform upon heat treatment into an interconnected porous network architecture
which is important for battery electrodes because such architectures possess a very large surface area for the storage of energy, a critical component to improving battery performance.
One of the problems with conventional carbons, such as graphite, is that they are prepared typically with chemicals such as acids
and activated by bases that are not environmentally friendly, said Mihri Ozkan, a professor of electrical and computer engineering.
Therefore, the UC Riverside team is focused on naturally-derived carbons, such as the skin of the caps of portabella mushrooms, for making batteries.
It is expected that nearly 900,000 tons of natural raw graphite would be needed for anode fabrication for nearly six million electric vehicle forecast to be built by 2020.
This requires that the graphite be treated with harsh chemicals, including hydrofluoric and sulfuric acids, a process that creates large quantities of hazardous waste.
The European union projects this process will be unsustainable in the future. The Ozkan research is supported by the University of California
Riverside. This paper involving mushrooms is published just over a year after the Ozkan labs developed a lithium-ion battery anode based on nanosilicon via beach sand as the natural raw material.
Ozkan team is currently working on the development of pouch prototype batteries based on nanosilicon anodes. The UCR Office of Technology Commercialization has filed patents for the inventions above o
#A Light touch: Embedded Optical Sensors Could Make Robotic Hands More Dexterous Optical sensors may be suited uniquely for use in robotic hands,
according to Carnegie mellon University researchers who have developed a three-fingered soft robotic hand with multiple embedded fiber optic sensors.
They also have created a new type of stretchable optical sensor. By using fiber optics, the researchers were embed able to 14 strain sensors into each of the fingers in the robotic hand,
giving it the ability to determine where its fingertips are in contact and to detect forces of less than a tenth of a newton.
The new stretchable optical sensing material not incorporated in this version of the hand, potentially could be used in a soft robotic skin to provide even more feedback. f you want robots to work autonomously
and to react safely to unexpected forces in everyday environments, you need robotic hands that have more sensors than is said typical today
Yong-Lae Park, assistant professor of robotics. uman skin contains thousands of tactile sensory units only in the fingertip
and a spider has hundreds of mechanoreceptors on each leg, but even a state-of-the-art humanoid such as NASA Robonaut has only 42 sensors in its hand and wrist.
Adding conventional pressure or force sensors is problematic because wiring can be complicated, prone to breaking and susceptible to interference from electric motors and other electromagnetic devices.
But a single optical fiber can contain several sensors; all of the sensors in each of the fingers of the CMU hand are connected with four fibers,
although, theoretically, a single fiber could do the job, Park said. And the optical sensors are impervious to electromagnetic interference.
The Carnegie mellon researchers will discuss the robotic hand, developed together with researchers at Intelligent Fiber optic Systems Corp.,with support from NASA, Sept. 29 at the IEEE International Conference on Intelligent Robots and Systems, IROS 2015, in Hamburg, Germany.
A report on the highly stretchable optical sensors will be presented Oct 1 at the same conference. f you want robots to work autonomously
and to react safely to unexpected forces in everyday environments, you need robotic hands that have more sensors than is typical today.
Yong-Lae Park Industrial robots, working in a controlled environment where people don venture, are capable of extremely precise manipulation with only limited sensors.
But as roboticists at CMU and elsewhere work to develop soft robots that can interact routinely and safely with humans,
increased attention to tactile and force sensing is said essential, Park. Each of the fingers on the robotic hand mimic the skeletal structure of a human finger, with a fingertip,
middle node and base node connected by joints. The skeletal onesare 3-D-printed hard plastic and incorporate eight sensors for detecting force.
Each of the three sections is covered with a soft silicone rubber skin embedded with a total of six sensors that detect where contact has been made.
A single active tendon works to bend the finger, while a passive elastic tendon provides opposing force to straighten the finger.
The hand, developed with mechanical engineering students Leo Jiang and Kevin Low, incorporates commercially available fiber Bragg grating (FBG) sensors,
which detect strain by measuring shifts in the wavelength of light reflected by the optical fiber.
Despite their advantages, conventional optical sensors don stretch much glass fibers stretch hardly at all and even polymer fibers stretch typically only 20-25 percent, Park noted.
That is a limiting factor in a device such as a hand where a wide range of motion is essential.
Park has developed previously highly stretchable microfluidic soft sensors membranes that measure strain via liquid-conductor-filled channels
but they are difficult to make and can cause a mess if the liquid leaks out.
So Park, working with mechanical engineering students Celeste To from CMU and Tess Lee Hellebrekers from the University of Texas, invented a highly stretchable and flexible optical sensor, using a combination of commercially available silicone rubbers.
These soft waveguides are lined with reflective gold; as the silicone is stretched, cracks develop in the reflective layer,
allowing light to escape. By measuring the loss of light, the researchers are able to calculate strain or other deformations.
Park said this type of flexible optical sensor could be incorporated into soft skins. Such a skin would
not only be able to detect contact, as is the case with the soft components in the CMU hand,
but also measure force
#Ground-breaking computer program diagnoses cancer in two days In the vast majority of cancer cases, the doctor can quickly identify the source of the disease, for example cancer of the liver, lungs, etc.
However, in about one in 20 cases, the doctor can confirm that the patient has cancerut cannot find the source.
These patients then face the prospect of a long wait with numerous diagnostic tests and attempts to locate the origin of the cancer before starting any treatment.
Now, researchers at DTU Systems Biology have combined genetics with computer science and created a new diagnostic technology based on advanced self learning computer algorithms whichn the basis of a biopsy from a metastasisan with 85 per cent certainty identify the source of the disease
and thus target treatment and, ultimately, improve the prognosis for the patient. Each year, about 35,000 people are diagnosed with cancer in Denmark,
and many of them face the prospect of a long wait until the cancer has been diagnosed and its source located.
However, even after very extensive tests, there will still be 2-3 per cent of patients where it has not been possible to find the origin of the cancer.
In such cases, the patient will be treated with a cocktail of chemotherapy instead of a more appropriately targeted treatment,
which could be more effective and gentler on the patient. Fast and accurate results The newly developed method
which researchers are calling Tumortracer, are based on analyses of DNA mutations in cancer tissue samples from patients with metastasized cancer,
i e. cancer which has spread. The pattern of mutations is analysed in a computer program which has been trained to find possible primary tumour localizations.
The method has been tested on many thousands of samples where the primary tumour was identified already, and it has proven extremely precise.
The next step will be to test the method on patients with unknown primary tumours. In recent years, researchers have discovered several ways of using genome sequencing of tumours to predict
whether an individual cancer patient will benefit from a specific type of medicine. This is a very effective method
and it is becoming increasingly common to conduct such sequencing for cancer patients. Associate professor Aron Eklund from DTU Systems Biology explains:
e are pleased very that we can now use the same sequencing data together with our new algorithms to provide a much faster diagnosis for cancer cases that are difficult to diagnose,
and to provide a useful diagnosis in cases which are currently impossible to diagnose. At the moment, it takes researchers two days to obtain a biopsy result,
but we expect this time to be reduced as it becomes possible to do the sequencing increasingly faster.
And it will be straightforward to integrate the method with the methods already being used by doctors.
Researchers expect that in the long term, the method can also be used to identify the source of free cancer cells from a blood sample,
and thus also as an effective and easy way of monitoring people who are at risk of developing cancer.
Read the scientific article Tumortracer: A method to identify the tissue of origin from the somatic mutations of a tumour specimen in BMC Medical Genomics i
#Scientists test new gene therapy for vision loss from a mitochondrial disease NIH-funded study shows success in targeting MITOCHONDRIAL DNA in mice Researchers funded by the National institutes of health have developed a novel mouse model for the vision disorder
Leber hereditary optic neuropathy (LHON), and found that they can use gene therapy to improve visual function in the mice.
LHON is one of many diseases tied to gene mutations that damage the tiny energy factories that power our cells,
called mitochondria. his study marks an important contribution to research on LHON, and in efforts toward an effective therapy.
But the implications are even broader because the approaches that the investigators used could aid therapy development for a vast array of other mitochondrial diseases,
said Maryann Redford, D d. S m. P. H.,a program director in Collaborative Clinical Research at NIH National Eye Institute,
which helped fund the study. Mitochondria are as complex as any modern manufacturing facility, with specialized machinery for converting nutrients and oxygen into cellular energy.
They even have their own DNA, and it is mutations within this MITOCHONDRIAL DNA (mtdna) that lead to LHON,
as well as a host of other diseases. But the unique nature of mtdna has presented challenges for developing
and testing potential therapies for such diseases. Until now here was no efficient way to get DNA into mitochondria,
said John Guy, M d.,professor of ophthalmology and director of the ocular gene therapy laboratory at the Bascom Palmer Eye Institute, University of Miami Miller School of medicine.
Dr. Guy laboratory is among the first to develop an approach that can target mtdna in living mice and people.
Their success in creating a mouse model of LHON and using it to test an investigational gene therapy is described today in the Proceedings of the National Academy of Sciences.
The global impact of LHON is unknown. In England the estimated prevalence is about 1 in 30,000.
Early symptoms include blurry vison and usually appear during the teens or early twenties. Eyesight tends to worsen over time,
eventually leading to a severe loss of sharpness (acuity) and color vision. These problems are caused by a loss of retinal ganglion cellshe cells that carry visual signals from the retina through the optic nerve and into the brain.
The most common mutation behind LHON impairs a mitochondrial gene called ND4. Dr. Guy began to research a possible gene therapy approach for delivering a substitute copy of the gene into mitochondria about 15 years ago.
In most studies and applications of gene therapy viruses have become the preferred vessel for delivering genes into cells.
But viruses evolved to invade the body cells and penetrate the nucleus, which contains the bulk of our DNA,
comprising about 20,000 genes. Most viruses are poor at penetrating mitochondria. To fix that, Dr. Guy
and his team took advantage of the fact that mitochondria import cellular proteins that they cannot make themselves.
By attaching a bit of one such protein to the outer shell of a virusalled an adeno-associated viruse effectively gave the virus a homing signal
and entry code into mitochondria. This modified virus has been the key to creating a mouse that replicates LHON and to an investigational gene therapy for LHON that is currently in clinical trials.
To create a mouse model for LHON, the researchers loaded the virus with a defective copy of the ND4 gene carrying the same mutation that causes about 70 percent of LHON cases.
They also included DNA coding for a red fluorescent protein, as a visible marker for the virus and its payload.
Then they injected the virus into fertilized mouse egg cells, and grew the cells to maturity.
After breeding the mice through several generations, the researchers had their mouse model. The presence of the virally encoded ND4 mutation in the eye was confirmed by essentially doing an eye exam to look for the red fluorescent marker.
Over time the mice showed a loss of retinal ganglion cells, atrophy (shrinkage) of the optic nerve,
and a decline in visual responses, as seen in a type of electrical recording from the retina known as an electroretinogram.
To develop a gene therapy for LHON, the team packaged the normal human ND4 gene into the same stealthy virus. This combination,
when injected into the eye, led to improved visual function in the LHON mouse model.
When injected into normal mice, the virus carrying ND4 did not cause any adverse effects on vision.
Prior to development of the new mouse model Dr. Guy lab had shown that they could produce temporary signs of LHON in mice.
They were able to prevent development of LHON in the mice, but not reverse it. ow wee shown that we can improve visual function after it been lost,
The mouse research is helping inform an ongoing NEI-supported clinical trial, which is led by Dr. Guy
and is testing the safety of the same gene therapy approach (without the red fluorescent protein) in people with LHON.
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