#Just hit'print':'Office inkjet printer could produce simple tool to identify infectious disease, food contaminants Consumers are one step closer to benefiting from packaging that could give simple text warnings
when food is contaminated with deadly pathogens like E coli and Salmonella, and patients could soon receive real-time diagnoses of infections such as C. difficile right in their doctors'offices,
saving critical time and trips to the lab. Researchers at Mcmaster University have developed a new way to print paper biosensors,
simplifying the diagnosis of many bacterial and respiratory infections. The new platform is the latest in a progression of paper-based screening technologies
which now enable users to generate a clear, simple answer in the form of letters and symbols that appear on the test paper to indicate the presence of infection or contamination in people, food or the environment."
"The simplicity of use makes the system easy and cheap to implement in the field
or in the doctor's office,"says John Brennan, director of Mcmaster's Biointerfaces Institute,
where the work was done with biochemist Yingfu Li and graduate student Carmen Carrasquilla.""Imagine being able to clearly identify contaminated meat, vegetables or fruit.
For patients suspected of having infectious diseases like C. diff, this technology allows doctors to quickly
and simply diagnose their illnesses, saving time and expediting what could be lifesaving treatments. This method can be extended to virtually any compound,
be it a small molecule, bacterial cell or virus, "he says. The research, in its formative stage, addresses a key problem facing current paper-based biosensing techniques which are labour-intensive, sometimes costly and inconvenient,
and often difficult to mass produce. Using state-of-the-art methods to produce"bio-inks""researchers can now use conventional office ink jet-printers printers to print human-made DNA molecules with very high molecular weight on paper, much like printing a letter in an office.
The sheer size of the DNA--which produces a signal when a specific disease biomarker is present--is enough to ensure it remains immobilized and therefore stable.
The paper sensor emerges from the printer ready to use, like ph paper. The implications are significant,
says Brennan, since the new technology could be used in many fields where quick answers to important questions are critical."
"We could conceivably adapt this for numerous applications which would include rapid detection of cancer
or monitoring toxins in the water supply,"says Brennan.""There are hundreds of possibilities
#Future electronics based on carbon nanotubes First of all they are tiny--on the atomic scale and perhaps near the physical limit of how small you can shrink a single electronic switch.
Like silicon, they can be semiconducting in nature, a fact that is essential for circuit boards, and they can undergo fast and highly controllable electrical switching.
But a big barrier to building useful electronics with carbon nanotubes has always been the fact that
when they're arrayed into films, a certain portion of them will act more like metals than semiconductors--an unforgiving flaw that fouls the film,
shorts the circuit and throws a wrench into the gears of any potential electronic device. In fact, according to University of Illinois-Urbana Champaign professor John Rogers, the purity needs to exceed 99.999 percent--meaning even one bad tube in 100,000 is enough to kill an electronic device."
"If you have lower purity than that, "he said, "that class of materials will not work for semiconducting circuits."
"Now Rogers and a team of researchers have shown how to strip out the metallic carbon nanotubes from arrays using a relatively simple,
scalable procedure that does not require expensive equipment. Their work is described this week in the Journal of Applied Physics, from AIP Publishing.
The Road to Purificationthough it has been a persistent problem for the last 10-15 years, the challenge of making uniform,
aligned arrays of carbon nanotubes packed with good densities on thin films has largely been solved by several different groups of scientists in recent years,
Rogers said. That just left the second problem which was to find a way to purify the material to make sure that none of the tubes were metallic in character--a thorny problem that had remained unsolved.
There were some methods of purification that were easy to do but fell far short of the level of purification necessary to make useful electronic components.
Very recent approaches offer the right level of purification but rely on expensive equipment, putting the process out of reach of most researchers.
As the team reports this week, they were able to deposit a thin coating of organic material directly on top of a sheet of arrayed nanotubes in contact with a sheet of metal.
They then applied current across the sheet which allowed the current to flow through the nanotubes that were metal conductors--but not the bulk of the tubes,
which were semiconducting. The current heated up the metal nanotubes a tiny amount--just enough to create a"thermal capillary flow"that opened up a trench in the organic topcoat above them.
Unprotected, the metallic tubes could then be etched away using a standard benchtop instrument, and then the organic topcoat could be washed away.
This left an electronic wafer coated with semiconducting nanotubes free of metallic contaminants, Rogers said. They tested it by building arrays of transistors
he said.""You end up with a device that can switch on and off as expected, based on purely semiconducting character,
"Rogers said d
#Alternating antibiotics could make resistant bacteria beatable Researchers from the University of Exeter has shown that the use of'sequential treatments'--using alternating doses of antibiotics--might offer effective treatment against bacterial infection.
Crucially, the research also demonstrates this technique for administering treatment also reduces the risk of the bacteria becoming resistant to antibiotics,
and so maintaining the long-term effectiveness of the drugs. The collaborative international research, led by Professor Robert Beardmore from the University of Exeter
and funded by EPSRC, is published in leading scientific journal PLOS Biology on Wednesday 8 april. The research indicates that drug treatments with two antibiotics can be designed to kill bacteria at dosages that would ordinarily cause rapid development of drug resistance and sustained bacterial growth,
when administered alone or in combination. The researchers used a test-tube model of a bacterial infection to show that,
even in bacteria that already harbour drug resistance genes, sequential treatments could deal with the bacteria, even when much higher doses of single drugs or mixtures of two drugs failed to do so."
"Our study finds a complex relationship between dose, bacterial population densities and drug resistance,"said lead author, Professor Beardmore."
"As we demonstrate, it is possible to reduce bacterial load to zero at dosages that are said usually to be sub lethal and,
therefore, are assumed to select for increased drug resistance.""The researchers also discovered that, although sequential treatments didn't suppress the rise of all drug resistance mutations in the bacteria,
one drug would'sensitize'the bacteria to the second drug, and therefore reduce the risk of resistance occurring.
Study co-author Dr Ayari Fuentes-Hernandez said:""Research has concentrated for decades on synergistic drug cocktails.
"While bacteria are masters at adapting to antibiotic challenge, this research suggests that there is a way to use this adaptation against them.
The fluctuating environments created by well-designed sequential treatments can sensitize bacteria and render them susceptible to concentrations of antibiotics that would normally induce drug resistance and continued existence.
although extensive further work is needed now to will be needed before sequential treatments make it in to the clinic,
#Biologists identify brain tumor weakness The study, led by researchers from the Whitehead Institute and MIT's Koch Institute for Integrative Cancer Research, found that a subset of glioblastoma tumor cells is dependent on a particular enzyme that breaks down the amino acid glycine.
Without this enzyme, toxic metabolic byproducts build up inside the tumor cells, and they die. Blocking this enzyme in glioblastoma cells could offer a new way to combat such tumors,
says Dohoon Kim, a postdoc at the Whitehead Institute and lead author of the study,
which appears in the April 8 online edition of Nature. David Sabatini a professor of biology at MIT and member of the Whitehead Institute, is the paper's senior author.
Matthew Vander Heiden, the Eisen and Chang Career development Associate professor of Biology and a member of the Koch Institute, also contributed to the research,
along with members of his lab. GLDC caught the researchers'attention as they investigated diseases known as"inborn errors of metabolism,
"which occur when cells are missing certain metabolic enzymes. Many of these disorders specifically affect brain development;
Such patients must avoid eating phenylalanine to prevent problems such as intellectual disability and seizures. Loss of GLDC produces a disorder called nonketotic hyperglycinemia,
which causes glycine to build up in the brain and can lead to severe mental retardation. GLDC is also often overactive in certain cells of glioblastoma,
the most common and most aggressive type of brain tumor found in humans. The researchers found that GLDC,
These regions are often found at the center of tumors, which are inaccessible to blood vessels.
It turns out that in this low-oxygen environment, SHMT2 gives cells a survival edge because it can indirectly influence the activity of an enzyme called PKM2,
which makes them better suited to survive in the ischemic tumor microenvironment, "Kim says. However, this highly active SHMT2 also produces a glut of glycine,
Without GLDC, glycine enters a different metabolic pathway that generates toxic products that accumulate and kill the cell.
#Study on new treatment for prostate cancer Published in The british Journal of Cancer (BJC), the study is the first time low temperature plasmas (LTPS) have been applied on cells grown directly from patient tissue samples.
It is the result of a unique collaboration between the York Plasma Institute in the Department of physics and the Cancer Research Unit (CRU) in York Department of biology.
Taking both healthy prostate cells and prostate cancer tissue cells from a single patient, the study allowed for direct comparison of the effectiveness of the treatment.
Scientists discovered that LTPS may be a potential option for treatment of patients with organ confined prostate cancer
and a viable, more cost-effective alternative to current radiotherapy and photodynamic therapy (PDT) treatments.
Low temperature plasmas are formed by applying a high electric field across a gas using an electrode, which breaks down the gas to form plasma.
This creates a complex, unique reactive environment containing high concentrations of reactive oxygen and nitrogen species (RONS).
Operated at atmospheric pressure and around room temperature, the delivery of RONS, when transferred through plasma to a target source,
is a key mediator of oxidative damage and cell death in biological systems. The way cell death occurs
when using LTP treatment is different from other therapies. The active agents in the LTP break up DNA
and destroy cells by necrosis, where cell membranes are ruptured, resulting in cell death. This is different to some current therapies
which cause apoptosis, where cells are prompted to die through natural mechanisms that can result in treatment resistance.
Adam Hirst a Phd student at the York Plasma Institute who has been working with Dr Fiona Frame on the project,
said: espite continual improvement and refinement, long term treatment for prostate cancer is recognised still as inadequate.
In the case of early stage organ confined tumours, patients may be treated with a focal therapy, for example cryotherapy, photodynamic therapy,
or radiotherapy. owever, around a third of patients will experience recurrence of their disease following radiotherapy.
This may be due to the inherent radio-resistance of a small fraction of the tumour the cancer stem-like cells.
Furthermore, numerous side effects are experienced often following treatment. hrough this research we have found that LTPS induce high levels of DNA damage
which leads in turn to a substantial reduction in colony forming ability, and ultimately necrotic cell death.
we have presented the first experimental evidence promoting the potential of LTP as a future focal cancer therapy treatment for patients with early stage prostate cancer.
monitoring the precision of plasma application. If all subsequent trials are successful, LTP could be used to treat cancer patients within 10-15 years 1
#Researchers deliver large particles into cells at high speed The researchers created a highly efficient automated tool that delivers nanoparticles, enzymes, antibodies, bacteria and other"large-sized"cargo into mammalian cells at the rate
of 100,000 cells per minute--significantly faster than current technology, which works at about one cell per minute.
The research, published online in Nature Methods on April 6, was led by Eric Pei-Yu Chiou, associate professor of mechanical and aerospace engineering and of bioengineering at the Henry Samueli School of engineering and Applied science.
Collaborators included students, staff and faculty members from the engineering school and the David Geffen School of medicine at UCLA. Currently
the only way to deliver so-called large cargo, particles up to 1 micrometer in size, into cells is by using micropipettes, syringe-like tools common in laboratories,
which is much slower than the new method. Other approaches for injecting materials into cells--such as using viruses as delivery vehicles
or chemical methods--are only useful for small molecules, which are typically several nanometers in length.
A nanometer is one one-thousandth of a micrometer. The new device, called a biophotonic laser-assisted surgery tool,
or BLAST, is a silicon chip with an array of micrometer-wide holes, each surrounded by an asymmetric, semicircular coating of titanium.
Underneath the holes is a well of liquid that includes the particles to be delivered. Researchers use a laser pulse to heat the titanium coating,
who is also a member of the California Nanosystems Institute. Inserting large cargo into cells could lead to scientific research that was previously not possible.
and help researchers study diseases caused by mutant MITOCHONDRIAL DNA. It also could help scientists dissect the function of genes involved in the lifecycle of pathogens that invade the cell
and understand the cell's defense mechanisms against them.""Now it doesn't matter the size
"The new information learned from these types of studies could assist in identifying pathogen targets for drug development,
or provide fundamental insight on how the pathogen-host interaction enables a productive infection or effective cellular response to occur,
"said Dr. Michael Teitell, chief of the division of pediatric and developmental pathology, and a co-author of the paper.
a single chip can provide enough data for a statistical analysis of how the cells respond in an experiment.
a former student of Chiou's who received his doctorate in December. Other UCLA authors were Ting-Hsiang Wu, a former doctoral student of Chiou's;
Dr. Daniel Clemens, adjunct professor of medicine; Bai-Yu Lee, an assistant researcher; Ximiao Wen, a graduate student in mechanical engineering;
and Dr. Marcus Horwitz, professor of medicine and of microbiology, immunology and molecular genetics. The research was supported by a University of California Discovery Biotechnology Award, the National institutes of health, Nanocav and the National Science Foundation n
#New understanding of electromagnetism could enable'antennas on a chip'A team of researchers from the University of Cambridge have unravelled one of the mysteries of electromagnetism,
which could enable the design of antennas small enough to be integrated into an electronic chip.
These ultra-small antennas--the so-called'last frontier'of semiconductor design--would be a massive leap forward for wireless communications.
In new results published in the journal Physical Review Letters, the researchers have proposed that electromagnetic waves are generated not only from the acceleration of electrons,
but also from a phenomenon known as symmetry breaking. In addition to the implications for wireless communications the discovery could help identify the points where theories of classical electromagnetism and quantum mechanics overlap.
The phenomenon of radiation due to electron acceleration, first identified more than a century ago, has no counterpart in quantum mechanics,
where electrons are assumed to jump from higher to lower energy states. These new observations of radiation resulting from broken symmetry of the electric field may provide some link between the two fields.
The purpose of any antenna, whether in a communications tower or a mobile phone, is to launch energy into free space in the form of electromagnetic or radio waves,
and to collect energy from free space to feed into the device. One of the biggest problems in modern electronics,
however, is that antennas are still quite big and incompatible with electronic circuits --which are ultra-small
and getting smaller all the time.""Antennas, or aerials, are one of the limiting factors when trying to make smaller and smaller systems,
since below a certain size, the losses become too great, "said Professor Gehan Amaratunga of Cambridge's Department of Engineering,
who led the research.""An aerial's size is determined by the wavelength associated with the transmission frequency of the application,
and in most cases it's a matter of finding a compromise between aerial size
and the characteristics required for that application.""Another challenge with aerials is that certain physical variables associated with radiation of energy are understood not well.
For example, there is still no well-defined mathematical model related to the operation of a practical aerial. Most of what we know about electromagnetic radiation comes from theories first proposed by James Clerk Maxwell in the 19th century,
which state that electromagnetic radiation is generated by accelerating electrons. However, this theory becomes problematic when dealing with radio wave emission from a dielectric solid, a material
which normally acts as an insulator, meaning that electrons are not free to move around. Despite this
dielectric resonators are used already as antennas in mobile phones, for example.""In dielectric aerials, the medium has high permittivity,
meaning that the velocity of the radio wave decreases as it enters the medium, "said Dr Dhiraj Sinha, the paper's lead author."
"Working with researchers from the National Physical Laboratory and Cambridge-based dielectric antenna company Antenova Ltd, the Cambridge team used thin films of piezoelectric materials, a type of insulator
these materials become not only efficient resonators, but efficient radiators as well, meaning that they can be used as aerials.
The researchers determined that the reason for this phenomenon is due to symmetry breaking of the electric field associated with the electron acceleration.
there is symmetry of the electric field. Symmetry breaking can also apply in cases such as a pair of parallel wires in which electrons can be accelerated by applying an oscillating electric field."
"In aerials, the symmetry of the electric field is broken'explicitly 'which leads to a pattern of electric field lines radiating out from a transmitter,
such as a two wire system in which the parallel geometry is broken, '"said Sinha. The researchers found that by subjecting the piezoelectric thin films to an asymmetric excitation,
the symmetry of the system is broken similarly, resulting in a corresponding symmetry breaking of the electric field,
and the generation of electromagnetic radiation. The electromagnetic radiation emitted from dielectric materials is due to accelerating electrons on the metallic electrodes attached to them
as Maxwell predicted, coupled with explicit symmetry breaking of the electric field.""If you want to use these materials to transmit energy,
you have to break the symmetry as well as have accelerating electrons--this is the missing piece of the puzzle of electromagnetic theory,
"said Amaratunga.""I'm not suggesting we've come up with some grand unified theory, but these results will aid understanding of how electromagnetism
and quantum mechanics cross over and join up. It opens up a whole set of possibilities to explore."
ubiquitous computing where almost everything in our homes and offices, from toasters to thermostats, is connected to the internet.
and the ability to fit an ultra-small aerial on an electronic chip would be a massive leap forward.
Piezoelectric materials can be made in thin film forms using materials such as lithium niobate, gallium nitride and gallium arsenide.
Gallium arsenide-based amplifiers and filters are already available on the market and this new discovery opens up new ways of integrating antennas on a chip along with other components."
"It's actually a very simple thing, when you boil it down, "said Sinha.""We've achieved a real application breakthrough,
having gained an understanding of how these devices work
#Breakthrough finds molecules that block previously'undruggable'protein tied to cancer The findings, which could lead to a new class of cancer drugs,
appear in the current issue of ACS Chemical Biology.""These are reported the first small-molecule Hur inhibitors that competitively disrupt Hur-RNA binding
and release the RNA, thus blocking Hur function as a tumor-promoting protein, "said Liang Xu, associate professor of molecular biosciences and corresponding author of the paper.
The results hold promise for treating a broad array of cancers in people. The researcher said Hur has been detected at high levels in almost every type of cancer tested,
including cancers of the colon, prostate, breast, brain, ovaries, pancreas and lung.""Hur inhibitors may be useful for many types of cancer,
"Xu said.""Since Hur is involved in many stem cell pathways, we expect Hur inhibitors will be active in inhibiting'cancer stem cells,
'or the seeds of cancer, which have been a current focus in the cancer drug discovery field."
"Hur has been studied for many years, but until now no direct Hur inhibitors have been discovered, according to Xu.""The initial compounds reported in this paper can be optimized further
and developed as a whole new class of cancer therapy, especially for cancer stem cells, "he said."
"The success of our study provides a first proof-of-principle that Hur is druggable,
which opens a new door for cancer drug discovery. Many other RNA BINDING-PROTEINS proteins like Hur, which are so far undruggable,
can also be tested for drug discovery using our strategy.""The research team evaluated about 6,
"A cancer-causing gene, or oncogene, makes RNA, which then makes an oncoprotein that causes cancer
or makes cancer cells hard to kill, or both,"Xu said.""This is the problem we're trying to overcome with precision medicine."
"The scientist said the Hur-RNA binding site is like a long, narrow groove, not a well-defined pocket seen in other druggable proteins targeted by many current cancer therapies."
"Hur tightly binds to RNA like a hand, "Xu said.""The Hur protein grabs the'rope
'--or the RNA--at a site called'ARE'on the rope. We aimed to find a small-molecule compound that makes the hand release the rope by competing with ARE of the RNA."
"The research took more than 3 1/2 years and involved the collaboration of chemists, cancer biologists, computer modeling experts, biochemists and biophysicists at KU--notably the labs of Xu, Jeffrey Aub in the Department of Medicinal Chemistry and Jon Tunge in the Department of chemistry.
Grants from the National institutes of health, along with funding from the state of Kansas, the Hall Family Foundation and Bold Aspiration funding from KU's Office of the Provost, supported the work.
For Xu, the findings are reflective of a personal commitment to improving odds for people diagnosed with cancer
the second-largest killer in the U s. after heart disease.""Trained as medical doctor and Ph d.,with both a grandfather and an uncle who died of cancer,
I devoted my career to cancer research and drug discovery--aiming to translate discovery in the lab into clinical therapy,
to help cancer patients and their families, "he said.""We hope to find a better therapy--and eventually a cure--for cancer
#Study revises theory of how PTEN, a critical tumor suppressor, shuts off growth signals Today,
scientists at Cold Spring Harbor Laboratory (CSHL) publish new evidence explaining precisely how the protein encoded by PTEN (called PTEN) works--specifically,
how it is recruited to particular locations in our cells where pro-growth signals need to be shut off.
The new evidence, assembled by a team led by CSHL Associate professor Lloyd Trotman, contradicts a long-held assumption about PTEN function,
and could help scientists design more effective drugs to counteract cancer's hallmark trait, uncontrolled cellular growth."
"A whole generation of cancer investigators, including me, has been taught that PTEN performs its crucial role at the plasma membrane,
which is what separates the inside of cells from the outside environment"Trotman explains. The exterior surface of the membrane is dotted with receptor molecules--switches
which growth factors can flip on from the outside to transmit growth cues into the cell's interior.
Normally, these switches are off, and no signals are transmitted. Every once in a while, however, a pro-growth-hormone molecule docks at a receptor on the surface, setting off a cascade of biochemical events inside the cell."
"With respect to growth, the brakes are normally on, "says Trotman. In the cell membrane, fatty molecules are decorated with the equivalent of traffic signals,
and"in the default mode, the light is red.""But when a growth factor switches on a receptor, special enzymes change the light embedded in the membrane from red to green.
literally bouncing off the walls of the cell in random fashion, "Trotman says.""Using super-resolution microscopy,
And in view of PTEN's critical role as a tumor suppressor, it's also important that the process we uncovered is controlled a one,
"Many observed facts"fall into place"with the new explanation of how PTEN works.""Now we understand this fundamental process.
--or decoded--the genes of patients with Neuromuscular Disease (NMD) and was then able to identify the genetic source,
or likely genetic source, of each child's symptoms, according to a study published April 8 in the journal Molecular genetics & Genomic medicine."
"In all six cases of myopathy, or muscle weakness, these children had undergone extensive, expensive and invasive testing--often over many years--without a successful diagnosis,
until they enrolled in our study, "said Dr. Lisa Baumbach-Reardon, an Associate professor of TGEN's Integrated Cancer Genomics Division and the study's senior author.
This is a prime example of the type of"personalized medicine"TGEN uses to zero in on diagnoses for patients,
and to help their physicians find the best possible treatments.""Our results demonstrate the diagnostic value of a comprehensive approach to genetic sequencing,
or disease-causing, genetic variants with a single, timely, affordable test.""In one of the six cases, TGEN researchers found a unique disease-causing variant,
or mutation, in the CACNA1S gene for a child with severe muscle weakness in addition to ophthalmoplegia,
or the inability to move his eyes. Properly functioning CACNA1S is essential for muscle movement.
"To our knowledge, this is the first reported case of severe congenital myopathy with ophthalmoplegia resulting from pathogenic variants in CACNA1S,
Learning the specific genetic cause of symptoms is a key step in finding new therapeutic drugs that could treat the patient's disease.
In another closely related case, TGEN's genetic testing found a pathogenic variant in the RYR1 gene in a case of calcium channel myopathy.
Five of the six cases involved patients under the care of Dr. Saunder Bernes, a neurologist at Barrow neurological institute at Phoenix Children's Hospital.
A sixth patient, under the care of Dr. Judith Hall at the University of British columbia, also underwent genetic sequencing at TGEN."
"Without this type of deep genetic analysis, we might never have discovered the source of each of these children's disease,
"said Dr. Bernes, whose young patients'previous tests included muscle biopsies, EMG, MRI, EKG and limited gene sequencing."
"Now we are in a much better position to find new treatments for these and other children with similar symptoms."
"In three of the six cases, the children had Collagen 6 myopathies, or weaknesses. Collagen is essential to holding together muscles, tendons, skin, cartilage and the disks between vertebras.
or disease-causing mutation, in the COL6A3 gene, or likely pathogenic variants in the COL6A6 gene.
In still another case, TGEN testing identified the genetic culprit of the child's muscle weakness as a pathogenic EMD variant associated with Emery-Dreifuss muscular dystrophy.
"Reporting these cases raises awareness about how often each child with muscle disease is unique,
requiring personalized medical treatment beginning with genetic diagnosis through sequencing like we perform at TGEN.""Dr. Hunter said."
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