#Uptake mechanisms of cytostatics discovered A good 18 months ago, researchers at the Max-Delbrück-Centrum für Molekulare Medizin (MDC) and the Leibniz-Institut für Molekulare Pharmakologie (FMP) discovered the molecular identity of VRAC.
and at least one relative, is believed also to play a role in cell division and cancer. Arrayin collaboration with Dutch colleagues, the authors now show how important VRAC is, particularly in cancer.
They investigated cell lines to determine the role played by VRAC and its subunits in the transport of cisplatin and carboplatin into the cell.
From the researchers'point of view, this goes some way into explaining why some people are resistant to some forms of cancer therapy.
In their experiments, the work group of Thomas Jentsch had switched systematically off different combinations of VRAC forming proteins.
"For a long time, there has indeed been a hypothesis that VRAC plays a decisive role in apoptosis
Arraythe recent study also confirmed the hypothesis concerning apoptosis. If the protein LRRC8A, vital for VRAC, was put out of action,
"The suppression of apoptosis is probably due to the fact that, in the absence of volume-regulating VRAC,
"This novel uptake mechanism could even be confirmed by clinical data in this study. Researchers led by Sven Rottenberg of the Cancer Research Centre in Amsterdam also identified LRRC8D as a relevant gene in a genome-wide screen for cellular cytostatic resistance.
They studied the genetic data of ovarian cancer patients, who had been treated with cisplatin or carboplatin, with regard to their survival time.
Tumour database analysis showed that reduced LRRC8D expression correlated with a decreased survival time in these patients.
Arrayso, does the absence of the VRAC protein promote therapy resistances?""The data suggest that LRRC8A
and LRRC8D are also clinically relevant resistance genes, although this finding still has to be substantiated through prospective studies,
"says basic researcher Jentsch. And what next?""Purely theoretically, it might be possible to find activators,
Apparently, the VRAC subunit LRRC8D is immensely important for the transport of the amino acid taurine,
By switching off LRRC8D, it will now be possible to specifically investigate physiological and pathological roles of taurine release by VRAC.
Scientists have experimented for decades with a class of catalysts known as zeolites that transform alcohols such as ethanol into higher-grade hydrocarbons.
As ORNL researchers were developing a new type of zeolite-based conversion technology, they found the underlying reaction unfolds in a different manner than previously thought."
The researchers'analysis found that this energy-consuming intermediary step is not necessary for the conversion to happen.
Instead, an energy-producing"hydrocarbon pool"mechanism allows the zeolite catalysts to directly produce longer hydrocarbon chains from the original alcohols."
and requires energy. We showed this step doesn't occur, and that the overall reaction is slightly exothermic."
The research, supported by DOE's Bioenergy Technologies Office, has implications for the energy efficiency and cost of catalytic upgrading technologies proposed for use in biorefineries.
Uncovering the mechanism behind the reaction helps support the potential economic viability of ORNL's direct biofuel-to-hydrocarbon conversion approach."
"Our method of direct conversion of ethanol offers a pathway to produce suitable hydrocarbon blend-stock that may be blended at a refinery to yield fuels such as gasoline, diesel and jet fuel or commodity chemicals,
#Researchers develop 3-D printing method for creating patient-specific medical devices A team of researchers at Northeastern University has developed an innovative 3-D printing technology that uses magnetic fields to shape composite materials
--mixes of plastics and ceramics--into patient-specific products. The biomedical devices they are developing will be both stronger and lighter than current models and,
with their customized design, ensure an appropriate fit. Their paper on the new technology appears in the Oct 23 issue of Nature Communications.
One specific application of this new technology is developing patient-specific catheters, especially for premature newborns.
Today's catheters only come in standard sizes and shapes which means they cannot accommodate the needs of all premature babies."
"With neonatal care, each baby is a different size, each baby has a different set of problems,
"says Randall Erb, assistant professor in the Department of Mechanical and Industrial Engineering and lead researcher on the project."
"If you can print a catheter whose geometry is specific to the individual patient, you can insert it up to a certain critical spot,
"Others have used composite materials in 3-D printing, says Joshua Martin, the doctoral candidate who helped design
is that it enables them to control how the ceramic fibers are arranged --and hence control the mechanical properties of the material itself.
such as customized miniature biomedical devices. Within a single patient-specific device, the corners, the curves,
and the holes must all be reinforced by ceramic fibers arranged in just the right configuration to make the device durable.
This is the strategy taken by many natural composites from bones to trees. Consider the structure of human bone.
Fibers of calcium phosphate, the mineral component of bone, are oriented naturally just so around the holes for blood vessels
"by taking really simple building blocks but organizing them in a fashion that results in really impressive mechanical properties."
Erb and Martin's 3-D printing method aligns each minuscule fiber in the direction that conforms precisely to the geometry of the item being printed."
000 Small Business Technology Transfer grant from the National institutes of health to develop the neonatal catheters with a local company."
"Another of our goals is to use calcium phosphate fibers and biocompatible plastics to design surgical implants."
"The magnets are the defining ingredient in their 3-D printing technology. Erb initially described their role in the composite-making process in a 2012 paper in the journal Science.
First the researchers"magnetize"the ceramic fibers by dusting them very lightly with iron oxide,
They then apply ultralow magnetic fields to individual sections of the composite material--the ceramic fibers immersed in liquid plastic--to align the fibers according to the exacting specifications dictated by the product they are printing."
"Magnetic fields are very easy to apply, "says Erb.""They're safe, and they penetrate not only our bodies--think of CT SCANS--but many other materials."
"Finally, in a process called"stereolithography,"they build the product, layer by layer, using a computer-controlled laser beam that hardens the plastic.
Each six-by-six inch layer takes a mere minute to complete.""I believe our research is opening a new frontier in materials science research,
"says Martin."For a long time, researchers have been trying to design better materials, but there's always been a gap between theory and experiment.
With this technology, we're finally scratching the surface where we can theoretically determine that a particular fiber architecture leads to improved mechanical properties
#3-D printed'building blocks'of Life scientists have developed a 3-D printing method capable of producing highly uniform'blocks'of embryonic stem cells.
These cells--capable of generating all cell types in the body--could be used as the'Lego bricks'to build tissue constructs, larger structures of tissues,
"The researchers, based at Tsinghua University, Beijing, China, and Drexel University, Philadelphia, USA, used extrusion-based 3-D printing to produce a grid-like 3-D structure to grow embryoid body that demonstrated cell viability
and rapid self-renewal for 7 days while maintaining high pluripotentcy.""Two other common methods of printing these cells are either two-dimensional (in a petri dish)
or via the'suspension'method (where a'stalagmite'of cells is built up by material being dropped via gravity.)"
providing the basic building blocks for other researchers to perform experiments on tissue regeneration and/or for drug screening studies."
"Our next step is to find out more about how we can vary the size of the embryoid body by changing the printing and structural parameters,
#DNA in blood can track cancer development, response in real time Scientists have shown for the first time that tumour DNA shed into the bloodstream can be used to track cancers in real time as they evolve
and respond to treatment, according to a new Cancer Research UK study published in the journal Nature Communications.
Over three years, researchers at the University of Cambridge took surgical tumour samples (biopsies) and blood samples from a patient with breast cancer that had already spread to other parts of her body.
They carefully studied small fragments of DNA from dying tumour cells that are shed into the blood
comparing them with DNA from the biopsy that was taken at the same point in time. The results show that the DNA in the blood samples matched up with that from the biopsies,
reflecting the same pattern and timing of genetic changes appearing as the cancer developed and responded to treatment.
The results provide the first proof-of-principle that analysing tumour DNA in the blood can accurately monitor cancer within the body.
Study author Professor Carlos Caldas, senior group leader at the Cancer Research UK Cambridge Institute, said:"
"This definitively shows that we can use blood-based DNA tests to track the progress of cancer in real time.
The findings could change the way we monitor patients, and may be especially important for people with cancers that are difficult to reach,
as taking a biopsy can sometimes be quite an invasive procedure.""The patient in the study had had breast cancer that already spread to a number of other organs.
The researchers--part of a collaborative team effort involving the Carlos Caldas and Nitzan Rozenfeld laboratories at the Cancer Research UK Cambridge Institute--were even able to distinguish between the different secondary cancers
and examine how each of the tumours was responding to treatment. Professor Caldas added:""We were able to use the blood tests to map out the disease as it progressed.
We now need to see if this works in more patients and other cancer types,
but this is an exciting first step.""Dr Kat Arney, science information manager at Cancer Research UK, said:"
"Spotting tumour DNA in the bloodstream is a really promising area of research, and has the potential to give doctors valuable clues about a patient's disease without having to take repeated tumour samples."
"For now, surgical biopsies still play an important role in diagnosing and monitoring cancers. But this work gives us a window into the future,
where we'll use less invasive techniques to track the disease in real time
#Sound waves levitate cells to detect stiffness changes that could signal disease Utah Valley University physicists are literally applying rocket science to the field of medical diagnostics.
With a few key changes, the researchers used a noninvasive ultrasonic technique originally developed to detect microscopic flaws in solid fuel rockets, such as space shuttle boosters,
to successfully detect cell stiffness changes associated with certain cancers and other diseases. Brian Patchett, a research assistant and instructor within the Department of physics at Utah Valley University, will describe the group's method,
which uses sound waves to manipulate and probe cells, during the Acoustical Society of America's Fall 2015 Meeting, held Nov 2-6, in Jacksonville, Fla.
The method combines a low-frequency ultrasonic wave to levitate the cells and confine them to a single layer within a fluid and a high-frequency ultrasonic wave to measure the cell's stiffness."
"An acoustic wave is a pressure wave so it travels as a wave of high and low pressure.
By trapping a sound wave between a transducer--such as a speaker--and a reflective surface, we can create a'standing wave'in the space between,
"explained Patchett.""This standing wave has stationary layers of high and low pressure, a k a.''anti-nodes, 'and areas,'the nodes'where the pressure remains the same."
"This standing wave allowed the group to acoustically levitate the cells and isolate them in manner similar to their natural state--as they would be within human tissue or the bloodstream.
Previous work in this realm relied on"growing the cell cultures in a Petri dish, which tends to deform the structure,
The significance of the group's work is that it focuses on an unexplored method of measuring the properties of cells
and how they change during the process of cancer and disease development.""The stiffness of the cell is the primary change detected with our high-frequency ultrasound;
and how it changes in certain diseases, "Patchett said. The group's method can also help distinguish between different types of cancer--such as aggressive breast cancer vs. less aggressive forms."
"By isolating the cells in a monolayer of fluid via acoustic levitation, we're providing a better method for the detection of cell stiffness,
"Patchett said.""This method can be used to explore the aspect of cells that changes during Alzheimer's disease, the metastasis of cancer,
or during the onset of autoimmune responses to better understand these conditions and provide insight into possible treatment methods."
By isolating the cells in a levitated monolayer, we hope to see these changes more clearly
"pointed out Timothy Doyle, lead scientist on the project and an assistant professor of physics at Utah Valley University.
As far as other applications, the group's method may find use in clinics, hospitals,
and surgical centers as a way to immediately detect and characterize cancer or other diseases."
"Our method identifies aggressive types of breast cancer, for example, while in the operating room,"Patchett noted.""Faster than current pathology methods, it will enable doctors to ensure speedier assessments
and more effective treatment plans for patients--personalized to their specific needs, which, in turn, will end up being more cost effective in the long term."
"In the near future, the group plans to apply their method to a wide range of biological materials,
which is part of the immune response to an illness.""We're collaborating with the Huntsman Cancer Institute--part of the University of Utah healthcare system--to explore various types of breast tissues under levitation to refine our pathology detection methods,
"Patchett said.""Our goal is to provide potentially lifesaving, personalized medical treatments based on our ability to quickly and effectively detect cancers and diseases in patients
#Preventing dental implant infections One million dental implants are inserted every year in Germany, and often they need to be replaced due to issues such as tissue infections caused by bacteria.
In the future, these infections will be prevented thanks to a new plasma implant coating that kills pathogens using silver ions.
Bacterial infection of a dental implant is dreaded a complication, as it carries with it a high risk of jawbone degeneration.
Implanting an artificial dental root sets off a race between infectious pathogens and the body's own cellular defenses.
If the bacteria win they form a biological film over the titanium to protect themselves from antibiotics.
Once the implant is colonized by germs, the result is an inflammatory reaction, which can result in bone atrophy.
To lower the risk of infection and improve the long-term effectiveness of the implant, researchers at the Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Bremen have developed a new type of implant coating in cooperation with industry partners.
The Dentaplas coating helps prevent the growth of bacteria, thus allowing the implant to properly take hold
and thereby form a faster and more permanent bond with the jawbone. The trick to this lies in combining surface materials that feature physical as well as chemical properties."
"We have given the Dentaplas coating a rough texture, which promotes cellular growth, in addition to combining it with a hydrophilic plasma polymer coating,
which attracts moisture, "says Dr. Ingo Grunwald, project manager at the IFAM. Researchers have integrated silver nanoparticles into the thin plasma polymer coating,
which is up to just 100 nanometers thick. The silver nanoparticles dissolve over a period of several weeks,
and during that time they continuously release small quantities of antimicrobial silver ions, which kill bacteria.
Three layers of protection"The Dentaplas system consists of three layers, with two plasma polymer layers surrounding a center layer of silver.
Within this structure a biocide reservoir is formed and the outermost layer releases the ions. This is beneficial because it prevents direct contact between the tissue and the silver particles,
which can be exposed toxic when,"says developer Dr. Dirk Salz. Researchers can tailor the silver concentration as well as the thickness of the layers and their porosity.
This allows the silver ions to penetrate the outermost plasma polymer layer over a set period of time deemed necessary to properly integrate the implant.
When the silver reservoir is exhausted, no more silver ions are released, thus avoiding any long-term toxic effects.
In trials using finished implants and titanium test samples the IFAM researchers demonstrated that the Dentaplas coating is not only antimicrobial but also fully biocompatible and sterilizable.
The test samples were coated using a plasma polymerization facility at the IFAM in Bremen. Researchers confirmed the mechanical stability
and robustness of the Dentaplas coating in trials using the lower jawbones of pigs taken from butcher shops.
Here, they subjected the Dentaplas coated implants to the rigors of being screwed into place using the instruments found in modern dental practices.
The Dentaplas coating passed this stress test with flying colors. Project partner and Fraunhofer spinoff Bio Gate AG successfully transferred the processes of coating the test samples
and titanium screws to its own production facilities. The medical technology company is also the manufacturer of the Dentaplas three-layer coating system.
A demonstration unit of the plasma polymer coating is currently available. Researchers will be presenting a dental implant featuring the Dentaplas coating at the MEDICA trade fair in Düsseldorf from November 16-19 at the joint Fraunhofer booth t
#Giant Burst of Tiny Organisms Discovered on Tree of Life It used to be that to find new forms of life,
all you had to do was take a walk in the woods. Now it not so simple.
The most conspicuous organisms have long since been cataloged and fixed on the tree of life, and the ones that remain undiscovered don give themselves up easily.
You could spend all day by the same watering hole with the best scientific instruments and come up with nothing.
Maybe it not surprising, then, that when discoveries do occur, they sometimes come in torrents. Find a different way of looking
and novel forms of life appear everywhere. A team of microbiologists based at the University of California, Berkeley, recently figured out one such new way of detecting life.
At a stroke, their work expanded the number of known typesr phylaf bacteria by nearly 50 percent,
a dramatic change that indicates just how many forms of life on earth have escaped our notice so far. ome of the branches in the tree of life had been noted before,
a student in the lab of Jill Banfield and lead author of the paper. ith this study we were able to fill in many gaps.
The basic structure of the current tree goes back 40 years to the microbiologist Carl Woese, who divided life into three domains:
director of the U s. Department of energy Joint Genome Institute. hen we got microscopes, and got microbes.
though the researcherssuccess also owes a debt to more basic technology. The team gathered water samples from a research site on the Colorado river near the town of Rifle
Colo. Before doing any sequencing, they passed the water through a pair of increasingly fine filtersith pores 0. 2 and 0. 1 microns wide
and sent it to the Joint Genome Institute for sequencing. What they got back was a mess.
when performing metagenomic analysisequencing scrambled genetic material from many organisms at once. The Berkeley team began the reassembly process with algorithms that assembled bits of the sequenced genetic code into slightly longer strings called contigs. ou no longer have tiny pieces of DNA,
you have bigger pieces, Brown said. hen you figure out which of these larger pieces are part of a single genome.
This part of the process, in which contigs are combined to reconstruct the genome sequence is called genome binning.
To execute it, the researchers relied on another set of algorithms, customized for the task by Itai Sharon,
a co-author of the study. They also assembled some of the genomes manually, making decisions about
what goes where based on the fact that some characteristics are consistent for a given genome.
For example, the percentage of Gs and Cs will be similar on any part of an organism DNA.
SEE ALSO: Energy & Sustainability: Bigger Cities Aren't Always Greener, Data Show Health: Pharma Watch:
Raising Awareness or Drumming Up Sales? Mind & Brain: Men Are attracted to Nonconformist Women Space:
Sun Accused of Stealing Planetary Objects from Another Star Technology: Introducing the First Vehicle Powered by Evaporation More Science:
Baby Chicks'Mental Number Line Looks like Ours When the assembly was complete, the researchers had eight full bacterial genomes
and 789 draft genomes that were roughly 90 percent complete. Some of the organisms had been glimpsed before;
many others were completely new. The reason no one had found these organisms before is that the traditional method used to search for small forms of life doesn work for everything.
because the genetic code it contains is unique for every organism. When confronted with a DNA stew,
like the one from the water samples in Rifle, scientists use substances called primers to draw out
rendering some organisms effectively invisible. he primers don work as well as people would like them to,
By reconstructing complete or nearly complete genomes, Brown and his collaborators were able to locate 16s rrna genes
All the organisms they found have very short genomes about one million base pairs (compare that to E coli,
requiring them to use fermentation to generate energy. They are also missing many basic biosynthetic pathways
300 to 1, 500 phyla that microbiologists estimate wel have once a complete accounting is finished.
and genome binning make Brown and Banfield optimistic, though, that it won be long before wee mapped them all. think that much of the tree of life will come into view in the next few years,
Banfield wrote in an email. Of course, no sooner do we think wee seen everything than we come up with a new way to see.
#3-D-Printed Device Helps Computers Solve Cocktail-party Problem Artificial-intelligence researchers have struggled long to make computers perform a task that is simple for humans:
It is called the ocktail-party problem Typical approaches to solving it have involved either systems with multiple microphones,
or complex artificial-intelligence algorithms that try to separate different voices on a recording. But the latest invention, described in this week Proceedings of the National Academy of Sciences,
is a simple 3d printed device that can pinpoint the origin of a sound without the need for any sophisticated electronics.
Openings around the edge channel sound through 36 passages towards a microphone in the middle. Each passage modifies the sound in a subtly different way as it travels towards the centreoughly
as if an equalizer with different settings were affecting the sound in each slice, explains senior author Steven Cummer, an electrical engineer at Duke university in Durham, North carolina a
#Simple Test Makes Blood-clot-busting Drug Safer Scientists in China have developed a fluorescent probe to detect both heparin and its major contaminant.
The sensor could make it easier to monitor the quality of heparin supplies. Heparin is used widely as an anticoagulant in cardiovascular surgery as well as in postoperative and long-term therapy.
Millions of patients are treated with it each year; in 2013 sales of low molecular weight heparin reached $6. 5 billion (£4. 2 billion.
Heparin doses must be maintained within a strict range because overdoses can have numerous side-effects, such as unusual bleeding and blood in the urine.
Purity is also an important issue. It is not unheard of for the contaminant oversulfated chondroitin sulfate (OSCS) to slip into the heparin supply chain.
but can lead to severe adverse reactions. 150 deaths between 2004 and 2008 in the US were thought to be a result of drug manufacturers deliberately cutting heparin with OSCS to save money.
And identifying OSCS in heparin currently requires methods such as high performance liquid chromatography combined with NMR and mass spectrometry,
and co-workers at Nanjing University in China to design a single fluorescent probe capable of detecting
Other biological molecules do not appear to interfere with the probe. Wei says the ethod could
Biosensors experts are enthusiastic about the sensor. Ben Zhong Tang from the Hong kong University of Science and Technology particularly likes the design
and envisages that his smart strategy will generate a large array of light up biosensors with outstanding performance.
And Kenneth Kam-Wing Lo from the City university of Hong kong says his interesting work will inspire the development of molecular probes and assays for biomolecules with high selectivity and sensitivity.
could significantly change the multibillion-dollar pain medication manufacturing business, but raises concerns about aggravating the growing problem of opioid abuse.
This same type of approach potentially also could be used to make other currently plant-based medicines for fighting cancer
infectious diseases and chronic illnesses. A similar"synthetic biology"technique is used already to make artemisenin, a key malaria-drug ingredient that was derived previously from trees (see Reuters story of August 12, 2014, http://reut. rs/1j2ovkj).
The scientists said they altered the yeast's genetic make-up in a way that coaxed the cells to convert sugar into two opioids-hydrocodone and thebaine-in three to five days."
"This is important because, with further development, it may provide an alternative supply for these essential medicines
and allow greater access for most of the global population that currently has insufficient access to pain medication,
"said Stanford university bioengineering professor Christina Smolke, who led the research published in the journal Science.
Overtext Web Module V3.0 Alpha
Copyright Semantic-Knowledge, 1994-2011