The method could lead to new ways to treat cancer, type 1 diabetes and viral infections as well as facilitating research into T-cell function.'
'Genome editing in human T-cells has been a notable challenge for the field, 'said lead author Dr Alexander Marson from the University of California, San francisco.'
'We have now been able to cut as well as paste pieces of the genome into human T-cells for the first time to our knowledge,
'he added. In the experiment, the team were able to disable a protein found on T-cells, called CXCR4,
resulting in those cells no longer being prone to invasion by the HIV virus. They also used CRISPR/Cas9 to shut down a protein found on T-cells, known as PD-1,
in this way, T-cells could be manipulated to control cancer or possibly eliminate a tumour entirely. CRISPR/Cas9 involves the identification of specific areas on the DNA.
which involves subjecting the cells to an electric field that temporarily makes their membranes permeable, allowing the CRISPR/Cas9 molecule to enter.
'It has been really challenging to get CRISPR to work in T-cells. This, in our hands, allows us to achieve a new level of efficiency for cutting
'said lead author Dr Nicholas Turner, a Consultant Medical Oncologist at the Royal Marsden NHS Foundation Trust.
The study, published in Science Translational Medicine, looked at 55 patients with early-diagnosed breast cancer,
who had undergone all surgery followed by chemotherapy. The researchers took blood samples from these patients every six months for two years to look for circulating tumour (ct) DNA.
7. 9 months before visible signs were picked up by clinics. After treatment, it is difficult to identify
the only difference being a small number of mutations responsible for causing the cells to become cancerous.
To overcome this, the scientists used a technique called'mutation tracking'a polymerase chain reaction (PCR) test
which is personalised to the mutations of an individual patient's cancer DNA. The test screened the blood for DNA with these mutations.
Any DNA in the blood with these mutations must have been released by cancer cells remaining after the initial round of treatment.
As well as being used to predict relapse, the test will allow scientists to track further mutations that develop in cancers over time,
the researchers say. This knowledge could help personalise treatment, as it would allow the tailoring of treatment to the genetic make-up of an individual's cancer.
Professor Paul Workman, Chief executive of the Institute of Cancer Research, London, said:''We are moving into an era of personalised medicine for cancer patients.
This test could help us stay a step ahead of cancer by monitoring the way it is changing
and picking treatments that exploit the weakness of the particular tumour.''Dr Nick Peel, from Cancer Research UK, said:'
'Finding less invasive ways of diagnosing and monitoring cancer is really important and blood samples have emerged as one possible way of gathering crucial information about a patient's disease.'
'He added:''But there is some way to go before this could be developed into a test that doctors could use routinely,
and doing so is never simple. l
#Breakthrough in rare disease that causes growth of second skeleton Scientists have developed a potential antibody treatment for the rare genetic disease fibrodysplasia ossificans progressiva (FOP), in
which muscle and soft tissue gradually turn to bone. The disease is known to be caused by mutations in the ACVR1 gene,
which codes for a receptor protein that controls bone and muscle development. The mutations make this protein much more active than usual, resulting in the formation of extra bones.
This process is accelerated even by very minor injuries in people with FOP, and this extra bony tissue slowly immobilises the body,
causing problems with eating, breathing and mobility and eventually death. Dr Sarah Hatsell and her colleagues at Regeneron found that the overactivity of the mutant receptor is caused by its altered response to the signalling molecule Activin-A this molecule normally makes AVCR1 less active,
but in FOP patients Activin-A increases the activity of the mutated ACVR1 receptor, driving bone growth.
This led Dr Hatsell's team to investigate whether blocking Activin-A from binding to the receptor protein could prevent the excessive bone growth seen in FOP patients.
They injected an antibody that blocks Activin-A into mice that had been engineered genetically to have symptoms similar to FOP.
Regeneron is currently performing preclinical safety testing and may eventually conduct clinical trials if a safe clinical trial can be designed.
because people with FOP are so sensitive to injuries; even a simple injection can trigger bone overgrowth.'
'We are very fortunate and grateful that not only did Regeneron make this basic science discovery,
as a biotechnology company with expertise in developing antibodies, they are in a position to act on it
whether this could lead to a meaningful therapy, 'said Betsy Bogard, director of global research development for the International FOP Association i
#'Flu severity'gene identified A key gene that governs the severity of influenza infections has been identified.
Scientists predict that this finding might lead to a new class of antiviral drugs capable of targeting a range of different infections, The british Science Festival heard last week.
By studying samples from the 2009 swine flu outbreak, researchers noticed a strong relationship between severity of influenza symptoms and variants in a gene called IFIT3.
and sometimes fatal, illness when they are infected with the influenza virus. Professor Paul Kellam of the Wellcome Trust Sanger Institute near Cambridge said:'
'When you have this variant you have a four-to fivefold increased chance of severe influenza
when exposed to a virus that is otherwise causing mild or no disease in the wider population.'
'IFIT3 works by strengthening cell walls to prevent viruses from entering and infecting the cell. This defence is impaired in people who carry the rs12552 gene variant.
Early signs are that drugs that increase the activity of IFIT3 may be effective treatments for other viral diseases as well.'
from flu to dengue and Ebola,'commented Professor Kellam.''We have broad-spectrum antibiotics that work against a range of bacteria...
This could lead to a broad-spectrum antiviral, though it would work by altering human cells rather than targeting the virus directly,
During flu epidemics, rapid testing for the rs12252 variant in hospital emergency departments could help to identify people at risk of developing severe influenza and prioritise them for treatment.
Using the test in healthy people could also lead to a personalised approach to influenza vaccination.
At present, an annual flu vaccine is recommended for groups such as the over-65s pregnant women and people with chronic medical conditions, who are believed to be at greater risk of influenza complications.
Identifying those who are genetically susceptible could help doctors to decide more accurately who should receive influenza vaccination n
#eyond revolutionary bioreactor-in-a-briefcase brings warzone production The project, sponsored by a coalition including Thermo Fisher, Pfizer,
and the US government, aims at warzone use but the tech could also be applied to public quarantines, personalised medicine,
and ultra-low cost vaccine manufacturing, says Govind Rao who leads the research at the University of Maryland, Baltimore County (UMBC) Center for Advanced Sensor Technology.
Speaking at Bioprocess International conference in Boston on Tuesday, Rao described the team breakthrough in large molecule manufacturing as eyond revolutionary my head is still spinning.?
Welcome to Betty Crocker bioprocessinghe portable tech relies on a cell-free expression platform from Thermo Fisher;
MBC students even simulated conditions where soldiers use their own body heat to trigger protein production.
and streptokinase cross three bioreactors. One-and-a-half hours and youe done. igarette pack reactorsrao team has created 3d printed designs for their next goal:
flat-chip bioreactors the size of cigarette packs for continuous processing. The scientists are also working on making purification portable.
and have discovered a elf-cleaving peptide a split NPU (Nostoc punctiforme) intein which leaves just one column.
Military experts believed current pharmaceutical supply methods to battlefields sometimes requiring airdrops were need obsolete, and to be replaced with manufacturing at the point of care specific threat response without requiring specific preparedness. ao told Tuesday conference moving biomanufacturing to the front lines echoes the decentralisation of pharma supply chains to civilians,
as healthcare increasingly moves from hospitals to patient homes with the advent of technology like home diabetes tests. perfect storm in healthcare is happening,
with costs going through the roof. The effects of high drug prices and bad press are said nsustainable he and as recent coverage shows
f we don respond, someone else will come and fix the problem.?Our goal is to leverage this
and replace this large manufacturing footprint that is the bread and butter of our industry today with a suitcase-sized device that will make GMP therapeutics at the point of care within a few hours. know it sounds completely nuts. ield tests
so have have produced G-CSF (Granulocyte-colony stimulating factor), Interferon, and antibodies using the tech.
The team still has to contend with a host of regulatory issues, and Rao recognised that this sort of expensive military medicine touches only he 0. 01 per cent.
But he said he hopes this high-end high-tech work will fund pharmaceutical projects with a wider reach.
Cell-free production tech could be used to produce low-cost vaccines tremendous paradigm shift is definitely comingas well as personalised medicines.
Any future civil quarantines in response to flu pandemics could also provide a ump-startto adoption of portable tech,
he said
#eyond revolutionary bioreactor-in-a-briefcase brings warzone production The project, sponsored by a coalition including Thermo Fisher, Pfizer,
and the US government, aims at warzone use but the tech could also be applied to public quarantines, personalised medicine,
and ultra-low cost vaccine manufacturing, says Govind Rao who leads the research at the University of Maryland, Baltimore County (UMBC) Center for Advanced Sensor Technology.
Speaking at Bioprocess International conference in Boston on Tuesday, Rao described the team breakthrough in large molecule manufacturing as eyond revolutionary my head is still spinning. elcome to Betty Crocker bioprocessing
The portable tech relies on a cell-free expression platform from Thermo Fisher; it lyophilises the contents of a cell, minus the nucleus. t incredible, said Rao,
UMBC students even simulated conditions where soldiers use their own body heat to trigger protein production.
and streptokinase cross three bioreactors. One-and-a-half hours and youe done. Cigarette pack reactors Rao team has created 3d printed designs for their next goal:
flat-chip bioreactors the size of cigarette packs for continuous processing. The scientists are also working on making purification portable.
They are aiming for a one-size-fits-all purification process to make the platform flexible,
and have discovered a elf-cleaving peptide a split NPU (Nostoc punctiforme) intein which leaves just one column.
Military experts believed current pharmaceutical supply methods to battlefields sometimes requiring airdrops were need obsolete, and to be replaced with manufacturing at the point of care specific threat response without requiring specific preparedness.
Rao told Tuesday conference moving biomanufacturing to the front lines echoes the decentralisation of pharma supply chains to civilians,
as healthcare increasingly moves from hospitals to patient homes with the advent of technology like home diabetes tests. perfect storm in healthcare is happening,
with costs going through the roof. The effects of high drug prices and bad press are said nsustainable he and as recent coverage shows,
f we don respond, someone else will come and fix the problem. ur goal is to leverage this
and butter of our industry today with a suitcase-sized device that will make GMP therapeutics at the point of care within a few hours. know it sounds completely nuts.
and antibodies using the tech. The team still has to contend with a host of regulatory issues
and Rao recognised that this sort of expensive military medicine touches only he 0. 01 per cent.
high-tech work will fund pharmaceutical projects with a wider reach. Cell-free production tech could be used to produce low-cost vaccines tremendous paradigm shift is definitely comingas well as personalised medicines.
Any future civil quarantines in response to flu pandemics could also provide a ump-startto adoption of portable tech,
he said s
#An Important Step in Artificial intelligence In what marks a significant step forward for artificial intelligence, researchers at UC Santa barbara have demonstrated the functionality of a simple artificial neural circuit.
For the first time, a circuit of about 100 artificial synapses was proved to perform a simple version of a typical human task:
but important step,"said Dmitri Strukov, a professor of electrical and computer engineering. With time and further progress, the circuitry may eventually be expanded
what computers would require far more time and energy to perform. What are these functions? Well, you're performing some of them right now.
As you read this, your brain is making countless split-second decisions about the letters and symbols you see,
Key to this technology is the memristor (a combination of"memory"and"resistor"),an electronic component
Unlike conventional transistors, which rely on the drift and diffusion of electrons and their holes through semiconducting material,
the resulting device would have to be loaded enormous with multitudes of transistors that would require far more energy."
"Classical computers will always find an ineluctable limit to efficient brain-like computation in their very architecture,
"This memristor-based technology relies on a completely different way inspired by biological brain to carry on computation."
however, many more memristors would be required to build more complex neural networks to do the same kinds of things we can do with barely any effort and energy,
Potential applications already exist for this emerging technology, such as medical imaging, the improvement of navigation systems or even for searches based on images rather than on text.
The energy-efficient compact circuitry the researchers are striving to create would also go a long way toward creating the kind of high-performance computers
and memory storage devices users will continue to seek long after the proliferation of digital transistors predicted by Moore's Law becomes too unwieldy for conventional electronics."
and giving a serious boost to future computers,"said Prezioso. In the meantime, the researchers will continue to improve the performance of the memristors,
The very next step would be to integrate a memristor neural network with conventional semiconductor technology,
Konstantin Likharev from the Department of physics and Astronomy at Stony Brook University also conducted research for this project.
University of California-Santa barbara Â
#Researcher Discovers Molecules That Kill Cancer, Protect Healthy Cells Researchers have identified new molecules that kill cancer cells
while protecting healthy cells and that could be used to treat a variety of different cancers.
The research shines a light on what happens to cells at the moment they become cancerous. The research and preclinical trial results were published this month as an open access article in EBIOMEDICINE,
a new joint research-clinical journal from the editors of Cell and The Lancet. Professor Qing-Bin Lu, from the University of Waterloo's Faculty of science, initiated a novel molecular-mechanism-based program to discover a new class of non-platinum-based-halogenated molecules that kill cancer cells
yet prevent healthy cells from being damaged. The most effective cancer drugs today may kill cancer cells, but they also kill healthy cells, causing severe side effects for patients in the process.
The technique is part of a potential new field of science developed by Professor Lu called femtomedicine (FMD),
which integrats the ultrafast laser with molecular biology and cell biology. Professor Lu has applied the tool to understand the molecular mechanisms that cause cancer at the very moment
when the DNA becomes damaged. He has used also it to investigate how radiation therapy and chemotherapy using chemical agents,
in particular the widely used platinum chemotherapeutic Cisplatin, work in treating a variety of cancers.""We know DNA damage is the initial step,
"said Professor Lu.""With the novel femtomedicine approach we can go back to the very beginning to find out what causes DNA damage in the first place, then mutation, and then cancer."
"By understanding more about the fundamental mechanisms of the diseases, Professor Lu preselected molecules most likely to be effective as anticancer agents.
In this case, he discovered a new family of non-platinum-based molecules similar in structure to Cisplatin
but containing no toxic platinum. Preclinical studies with various cultured human cells as well as on rodents show that these new molecules are effective against cervical,
breast, ovarian, and lung cancers. Cisplatin, discovered more than 40 years ago, is an important, widely used platinum-based anticancer agent.
Unfortunately, the inclusion of platinum in the molecule causes serious side effects like neurotoxicity kidney damage, hearing loss, nausea and vomiting."
"It is extremely rare to discover anticancer agents that can selectively kill cancer cells and protect healthy cells,
as well as being effective in treating many different types of cancer and having a novel molecular mechanism of action.
"said Professor Lu. Professor Lu has applied already for patents on the new family of non-platinum-based-halogenated molecules that he has discovered
and hopes to start clinical trials soon. Source: University of Waterlo o
#Researchers Find New Target for Anti-Malaria Drugs A new target for drug development in the fight against the deadly disease malaria has been discovered by researchers at MIT.
In a paper published in the journal Cell Host & Microbe, the researchers describe how they identified the drug target
while studying the way in which the parasites Toxoplasma gondii, which causes toxoplasmosis, and Plasmodium, which causes malaria, access vital nutrients from their host cells.
Around one-third of the world deadly infectious diseases, including malaria and tuberculosis, are caused by pathogens that spend a large portion of their life inside specially built compartments within their host cells.
These compartments known as arasitophorous vacuoles, separate the host cytoplasm and the parasite by a membrane,
and thereby protect the parasites from the host cell defenses. They also provide an environment tailored to their needs, according to Dan Gold,
a postdoc who led the research in the laboratory of Jeroen Saeij, the Robert A. Swanson Career development Associate professor of Life sciences in MIT Department of biology.
However, the membrane of these vacuoles also acts as a barrier between the parasite and the host cell.
This makes it more difficult for the parasite to release proteins involved in the transformation of the host cell beyond the membrane in order to spread the disease
and for the pathogen to gain access to vital nutrients, Gold said. ltimately what defines a parasite is that they require certain key nutrients from their host,
he said. o they have had to evolve ways to get around their own barriers, to gain access to these nutrients.
Similar research into how the related Plasmodium pathogen performs this trick had identified a so-called rotein export complexthat transports encoded proteins from the parasite into its host red blood cell,
which transforms these red blood cells in a way that is vital to the spread of malaria. he clinical symptoms of malaria are dependent on this process
they could be used as a drug target against the diseases they cause, including malaria, he said. his very strongly suggests that you could find small-molecule drugs to target these pores,
which would be very damaging to these parasites, but likely wouldn have any interaction with any human molecules,
In addition to malaria the technique could also be used to target the parasite Eimeria, which affects cattle and poultry, among other animals,
and therefore has a huge economic cost, Gold said. This ery excitingresearch elegantly identifies a molecular component of a pore in the vacuole that separates the growing Toxoplasma parasite from its host cell to help in the acquisition of nutrients, according to Manoj Duraisingh,
a professor of immunology and infectious diseases at Harvard School of Public health who was involved not in the research. trikingly,
#Diagnosing Sepsis through Genetic Signature Investigators at the Stanford university School of medicine have identified a pattern of gene activity that could help scientists create a blood test for quickly
Sepsis is a whole-body inflammation syndrome set off when the immune system wildly overreacts to the presence of infectious pathogens.
The great majority of sepsis cases are caused by bacterial rather than viral infections and are treated best with antibiotics.
when a patient has an outwardly similar but infection-free syndrome called sterile inflammation, an intense, systemic inflammatory response to traumatic injuries, surgery,
blood clots or other noninfectious causes. t critical for clinicians to diagnose sepsis accurately and quickly,
said Purvesh Khatri, Ph d.,assistant professor of biomedical informatics research. Sepsis or sterile inflammation? In practice, distinguishing sepsis from sterile inflammation is a toss-up.
Right now, the only diagnostics that can help do this are too slow or too inaccurate,
or both, Khatri said. As a result, hospital clinicians are pressured to treat anybody showing signs of systemic inflammation with antibiotics.
The inability to easily distinguish sepsis from sterile inflammation makes it tough for pharmaceutical companies to conduct clinical trials of drugs aimed at treating sepsis;
patients may be assumed mistakenly to have sepsis when they in fact have sterile inflammation, and vice versa, Khatri said. e think wee got the makings of a diagnostic blood test that will allow clinicians to distinguish between these two types of inflammation,
Khatri is the senior author of the new study, published May 13 in Science Translational Medicine, in
and his associates to tease out a gene-activation pattern that distinguishes septic from sterile systemic inflammation. e thought there might be some genes that the body turns on specifically in response to infection,
and after sifting through a huge amount of data we found them, said lead author Timothy Sweeney, M d.,Ph d,
. a postdoctoral scholar now doing a residency in general surgery at Stanford. Numerous studies have been conducted to find differences in the activation levels of immune-response genes between infection-related inflammation and sterile inflammation.
But these studies have yielded conflicting or murky results. One big reason is that both infection
and noninfectious tissue trauma activate many of the same immune-system components and pathways. At the gene-activation level, the overlap is staggering:
whether due to sepsis or sterile causes. That overlap obscures any easily detectable changes attributable solely to infection.
Needle in a haystack Further confounding attempts to identify patterns of increases or decreases in gene activity is that fact that some patients are already experiencing sepsis
when theye admitted to the hospital, while others become infected during their hospital stay. So two different sepsis patients admitted at the same time may be at very different stages of a complex inflammation process. ow do you figure out which tiny fraction of those changes was caused by infection?
Youe looking for a needle in a haystack, Khatri said. The needle, it turns out,
consists of a signature formed by consistent changes in the activity levels of a mere 11 genes amid the chaotic background of the other 20,000-plus genes
The Stanford sleuths analyzed a number of publicly available data sets containing results of studies that had assessed activity levels for the entire human genome in sepsis cases,
600 patients in 27 different data sets containing medical information on diverse patient groups men and women, young and old,
suffering from sterile inflammation or sepsis, including patients who already had sepsis when first admitted to the hospital as well as patients who were diagnosed with it later in addition to healthy control subjects.
The analysis consisted of two separate steps. First, the researchers scoured nine data sets containing more than 650 patient samples.
in patients within 24 hours of a sepsis diagnosis compared with genes from those not diagnosed with sepsis.
following a surgery or injury, in inflammation-related gene activity over time, independent of the presence or absence of infection.
therefore time according to how soon a blood sample was drawn after the initial injury or surgery.
11 genes jumped out of the haystack as likely sepsis markers. The researchers confirmed this 11-gene signature in an additional 18 cohorts comprising more than 1,
800 patient samples. e were able to identify a slight bump in activity of these 11 genes in patients two to five days prior to their clinical diagnosis,
That could mean getting an earlier diagnosis than can be achieved with current approaches, which is key considering the rapid rate at which sepsis mortality rises once it gets a foothold.
The gene-activation signature showed a sepsis-detecting accuracy surpassing that of methods now in use
Sweeney said. Combining the new technique with other current diagnostic methods is likely to be more accurate than using any one alone,
Undergraduate student Aaditya Shidham is another Stanford co-author of the study. The study was funded by the Stanford Department of Surgery and by the National Library of Medicine and the National Institute of Allergy and Infectious diseases.
Source: Stanford Universit D
#New Device May Allow Sensations in Prosthetic Hands To the nearly 2 million people in the United states living with the loss of a limb,
A team of engineers and researchers at Washington University in St louis is working to change that
Daniel Moran, Ph d.,professor of biomedical engineering in the School of engineering & Applied science and of neurobiology, of physical therapy and of neurological surgery at Washington University School of medicine in St louis
If it works, upper-limb amputees who use motorized prosthetic devices would be able to feel various sensations through the prosthetic,
who received a prosthetic after losing his right hand in an epic battle with Darth Vader.
While the advanced prosthetic arm allows users to perform six different grips, such as picking up small objects,
it does not provide users with the sense of touch and orientation of a natural hand. DARPA is already funding the uke Arm,
who received a prosthetic after losing his right hand in an epic battle with Darth Vader.
While the advanced prosthetic arm allows users to perform six different grips such as picking up small objects, it does not provide users with the sense of touch and orientation of a natural hand.
Moran, whose expertise is in motor neurophysiology and brain-computer interfaces, and his team have developed an electrode designed to stimulate sensory nerve cells in the ulnar and median nerves in the arms.
The ulnar nerve, one of three main nerves in the forearm, is the largest nerve in the body unprotected by muscle
or bone and is connected to the ring finger and pinkie finger on the hand. It the nerve that is stimulated when a hit to the elbow triggers the unny bone.
The median nerve in the upper arm and shoulder is connected to the other fingers on the hand so together,
place the fingers of the prosthesis around it and lift it. They are unable to feel
users will have more control over the prosthesis. Moran team includes Harold Burton, Ph d.,professor of neurobiology and Wilson (Zach) Ray, M d.,assistant professor of neurological surgery, both at the School of medicine;
and Matthew Macewen, who graduatesthis month with an M d./Ph d. and who worked on this project for his dissertation.
Ray also will implant a small cuff electrode, the current standard of care, to compare the performance.
Once implanted, Moran and the team will train the nonhuman primates to play a joystick-controlled videogame, in
which the team will give them cues as to where to move the joystick by stimulating specific sectors in the ulnar and median nerves
In particular, Moran and the team will analyze how many different independent channels they can stimulate on the nerve to determine how many sensors will work on the prosthetic hand.
they can move different amounts of current around the nerve to activate different sectors to connect the touch sensors on the hand to a different sector on the nerve.
His team has had already success with this method in motor neurons in a rat model. f this works to stimulate motor neurons in muscles,
Burton, an expert in sensory neurophysiology, will analyze how the brain processes the feedback from the nerve stimulation. he more real estate the brain uses,
so there should be a lot of bandwidth. We think wel be able to send a lot of information to it.
Moran and his team will work with DARPA to determine how many sensors to put on the prosthetic hands. f the nervous system can handle more than eight
he said. e want to find the bandwidth and what the nervous system can interpret with artificial sensation. ource:
Washington University in St. Loui i
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