online genetic research tool"This work actually started mainly because of the demand of MU scientists, "said Jianlin Cheng, an associate professor of computer science in the MU College of Engineering."
"RNA sequencing is the means by which researchers use modern sequencing techniques to study RNA, or ribonucleic acid.
The process has increased the speed that researchers can note the differences in gene expression among genomes
Often, scientists must sift through incredibly large amounts of data to get to usable results. RNAMINER has cut that time drastically."
"Cheng and doctoral students Jilong Li and Jie Hou partnered with members of the MU Center for Botanical Interaction Studies, the Division of Biological sciences, the Department of chemistry, the Department of Biochemistry,
the MU Informatics Institute and the Bond Life sciences Center to analyze vast genomic data sets and to formulate the design of RNAMINER.
The website was created to be user friendly and allows users to upload data, analyze it through as many as five steps against the complete genomes of five species:
human, mouse, Drosophila melanogaster (a type of fly), TAIR10 arabidopsis (a small flowering plant) and Clostridium perfringens (a type of bacterium.
Genomic data for any species is welcome for upload to grow the database. On average, two gigabytes of data takes approximately 10 hours for the servers to process
and analyze. Most researchers get results within a couple of hours, Cheng said.""To use our pipeline,
you don't have to know about computing tools, "Cheng said.""You just need to upload files
and select several parameters, and it will automatically give those results. Using this raw data, we can compress that basically hundreds of thousands of times, even one million times,
and make the connections needed for our collaborators to identify the genes that cause diseases
In the first days of reprogramming mouse cells, the researchers observed that their production of netrin-1 was reduced strongly.
This time, the quantity of ips cells produced from mouse cells was much more greater.
from which fifteen times more ips cells were produced by adding netrin-1. From a therapeutic point of view,
#Bonelike 3-D silicon synthesized for potential use with medical devices"Using bone formation as a guide,
"Array"This opens up a new opportunity for building electronics for enhanced sensing and stimulation at bio-interfaces,"said lead author Zhiqiang Luo, a postdoctoral scholar in Tian's laboratory.
The team achieved three advances in the development of semiconductor and biological materials. One advance was the demonstration, by strictly chemical means, of three-dimensional lithography.
Existing lithographic techniques create features over flat surfaces. The laboratory system mimics the natural reaction-diffusion process that leads to symmetry-breaking forms in nature:
to promote the growth of silicon nanowires and to induce gold-based patterns in the silicon.
"The idea of utilizing deposition-diffusion cycles can be applied to synthesizing more complex 3d semiconductors,
Arraythe semiconductor industry uses wet chemical etching with an etch-resist to create planar patterns on silicon wafers.
This method also applies to the 3d lithography of many other semiconductor compounds.""This is a fundamentally new mechanism for etch mask
The testing showed that the synthetic silicon spicules displayed stronger interactions with collagen fibers--a skin-like stand-in for biological tissue--than did currently available silicon structures.
and the other silicon structures into the collagen fibers, then pulled them out. An Atomic Force Microscope measured the force required to accomplish each action."
"One of the major hurdles in the area of bioelectronics or implants is that the interface between the electronic device
#Gene therapy restores hearing in deaf mice Using gene therapy, researchers at Boston Children's Hospital and Harvard Medical school have restored hearing in mice with a genetic form of deafness.
Their work, published online July 8 by the journal Science Translational Medicine, could pave the way for gene therapy in people with hearing loss caused by genetic mutations."
"Our gene therapy protocol is not yet ready for clinical trials--we need to tweak it a bit more
--but in the not-too-distant future we think it could be developed for therapeutic use in humans,
"says Jeffrey Holt, Phd, a scientist in the Department of Otolaryngology and F. M. Kirby Neurobiology Center at Boston Children's and an associate professor of Otolaryngology at Harvard Medical school.
More than 70 different genes are known to cause deafness when mutated. Holt, with first author Charles Askew and colleagues at École Polytechnique Fédérale de Lausanne in Switzerland
focused on a gene called TMC1. They chose TMC1 because it is a common cause of genetic deafness, accounting for 4 to 8 percent of cases,
and encodes a protein that plays a central role in hearing, helping convert sound into electrical signals that travel to the brain.
The researchers tested gene therapy in two types of mutant mice. One type had the TMC1 gene completely deleted,
and is a good model for recessive TMC1 mutations in humans: Children with two mutant copies of TMC1 have profound hearing loss from a very young age, usually by around 2 years.
The other type of mouse, called Beethoven, has a specific TMC1 mutation--a change in a single amino acid
--and is a good model for the dominant form of TMC1-related deafness. In this form, less common than the recessive form, a single copy of the mutation causes children to gradually go deaf beginning around the age of 10 to 15 years.
To deliver the healthy gene, the team inserted it into an engineered virus called adeno-associated virus 1,
or AAV1, together with a promoter--a genetic sequence that turns the gene on only in certain sensory cells of the inner ear known as hair cells.
They then injected the gene-bearing AAV1 into the inner ear, with these findings: In the recessive deafness model, gene therapy with TMC1 restored the ability of sensory hair cells to respond to sound--producing a measurable electrical current--and also restored activity in the auditory portion of the brainstem.
Most importantly, the deaf mice regained their ability to hear. To test hearing, the researchers placed the mice in a"startle box
"and sounded abrupt, loud tones.""Mice with TMC1 mutations will just sit there, but with gene therapy, they jump as high as a normal mouse,
"says Holt. The force of their jump was measured by a plate on the floor underneath them;
it was detectable at sounds beginning around 80 decibels. In the dominant deafness model, gene therapy with a related gene, TMC2, was successful at the cellular and brain level,
and partially successful at restoring actual hearing in the startle test. Clinical trials on the horizon AAV1 is considered safe as a viral vector
and is already in use in human gene therapy trials for blindness, heart disease, muscular dystrophy and other conditions.
Holt hopes to partner with clinicians at Boston Children's Department of Otolaryngology and elsewhere to start clinical trials of TMC1 gene therapy within 5 to 10 years."
"Current therapies for profound hearing loss like that caused by the recessive form of TMC1 are hearing aids,
and cochlear implants,"says Margaret Kenna, MD, MPH, a specialist in genetic hearing loss at Boston Children's Hospital who is familiar with the work."
"Cochlear implants are great, but your own hearing is better in terms of range of frequencies, nuance for hearing voices, music and background noise,
and figuring out which direction a sound is coming from. Anything that could stabilize or improve native hearing at an early age is really exciting
"Holt believes that other forms of genetic deafness may also be amenable to the same gene therapy strategy.
Overall, severe to profound hearing loss in both ears affects 1 to 3 per 1, 000 live births.""I can envision patients with deafness having their genome sequenced and a tailored,
precision medicine treatment injected into their ears to restore hearing, "Holt says. Sound transducers: How TMC works Holt's team showed in 2013 that TMC1
and the related protein TMC2 are critical for hearing, ending a rigorous 30-year search by scientists.
Sensory hair cells in the inner ear contain tiny projections called microvilli, each with a channel at its tip formed by TMC1 and TMC2 proteins.
a mutation in the TMC1 gene is sufficient to cause deafness. However, Holt's study also showed that gene therapy with TMC2 could compensate for loss of a functional TMC1 gene,
restoring hearing in the recessive deafness model and partial hearing in the dominant deafness model."
"This is a great example of how the basic science can lead to clinical therapies, "says Holt."
"The implications of successful gene therapy are profound, and we are delighted to be associated with this study program,
"says Ernesto Bertarelli, co-chair of the Bertarelli Foundation, the primary funder of the research."
"These findings mark a defining moment in the way we understand, and can ultimately challenge, the burden of deafness in humans.
The results are testament to the immense dedication of the research team and their commitment to bringing best-in-class science ever closer to real-world application. i
Signal processing in the intracellular domain of the precursor-protein-producing cells is responsible for modifications that likely induce a relative positional change of the dimerization partners and
The latest publication in the Journal of Biological Chemistry now was nominated as one of the best 50 out of this year's 6
the intracellular signal processing for single precursor proteins may be inhibited in order to specifically knock out the growth factors required by individual cancer types s
#Cell structure discovery advances understanding of cancer development A cell structure has been discovered that could help scientists understand why some cancers develop.
For the first time, a structure called'the mesh'has been identified which helps to hold together cells. This discovery changes our understanding of the cell's internal scaffolding.
which is found to change in certain cancers, such as those of the breast and bladder.
associate professor and senior Cancer Research UK Fellow at the division of biomedical cell biology at Warwick Medical school.
"As a cell biologist you dream of finding a new structure in cells but it's so unlikely.
"Researchers at the University's Warwick Medical school made the discovery by accident while looking at gaps between microtubules
'In dividing cells, these gaps are incredibly small at just 25 nanometres wide--3, 000 times thinner than a human hair.
One of Dr Royle's Phd students was examining structures called mitotic spindles in dividing cells using a technique called tomography
which is like a hospital CAT SCAN but on a much smaller scale. This meant that they could see the structure which they later named the mesh.
when they divide each new cell has a complete genome. Mitotic spindles are made of microtubules
While"inter-microtubule bridges"in the mitotic spindle had been seen before, the researchers were the first to view the mesh.
and support from Cancer Research UK and North West Cancer Research. Dr Royle said:""We had been looking in 2d
and this gave the impression that'bridges'linked microtubules together. This had been known since the 1970s.
All of a sudden, tilting the fibre in 3d showed us that the bridges were not single struts at all
A cell needs to share chromosomes accurately when it divides otherwise the two new cells can end up with the wrong number of chromosomes.
This is called aneuploidy and this has been linked to a range of tumours in different body organs.
The mitotic spindle is responsible for sharing the chromosomes and the researchers at the University believe that the mesh is needed to give structural support.
Too little support from the mesh and the spindle will be too weak to work properly, however too much support will result in it being unable to correct mistakes.
TACC3, is overproduced in certain cancers. When this situation was mimicked in the lab, the mesh and microtubules were altered
and cells had trouble sharing chromosomes during division. Dr Emma Smith, senior science communications officer at Cancer Research UK, said:"
"Problems in cell division are common in cancer-cells frequently end up with the wrong number of chromosomes.
This early research provides the first glimpse of a structure that helps share out a cell's chromosomes correctly
when it divides, and it might be a crucial insight into why this process becomes faulty in cancer
and whether drugs could be developed to stop it from happening.""North West Cancer Research (NWCR) has funded the research as part of a collaborative project between the University of Warwick and the University of Liverpool,
where part of the research is being carried out. Anne Jackson, CEO at NWCR, said:""Dr Royle and Professor Ian Prior at the University of Liverpool have made significant inroads into our understanding of the way in
which cancer cells behave, which could potentially better inform future cancer therapies.""As a charity we fund only the highest standard of research,
as evidenced by Dr Royle's work.""All our funded projects undergo a thorough peer review process,
before they are considered by our scientific committee. Our specially selected scientific committee includes some of the UK's leading professors,
award-winning scientists and pioneering professionals
#Gene therapy advance thwarts brain cancer in rats Researchers funded by the National Institute of Biomedical Imaging
and Bioengineering have designed a nanoparticle transport system for gene delivery that destroys deadly brain gliomas in a rat model,
significantly extending the lives of the treated animals. The nanoparticles are filled with genes for an enzyme that converts a prodrug called ganciclovir into a potent destroyer of the glioma cells.
Glioma is one of the most lethal human cancers, with a five year survival rate of just 12,
%and no reliable treatment. Advances in the understanding of the molecular processes that cause these tumors has resulted in therapies aimed at delivering specific genes into tumors--genes that make proteins to kill
or suppress the growth of the tumor. Currently this approach relies heavily on using viruses to deliver the anti-tumor genes into the target cancer cells.
Unfortunately, viral delivery poses significant safety risks including toxicity, activation of the patient's immune system against the virus,
and the possibility of the virus itself encouraging tumors to develop.""Efforts to treat glioma with traditional drug
and radiation therapies have not been very successful, "says Jessica Tucker, Ph d.,NIBIB Director for the Program in Gene and Drug Delivery Systems and Devices."
"The ability to successfully deliver genes using these biodegradable nanoparticles, rather than potentially harmful viruses, is a significant step that reinvigorates the potential for gene therapy to treat deadly gliomas as well as other cancers."
"Jordan Green, Ph d.,of the Johns hopkins university School of medicine Biomedical engineering Department and a senior author of the work,
and his international team describe their findings in the February 24 issue of ACS Nano. The collaborators include colleagues from the Johns hopkins university School of medicine Departments of Neurosurgery, Oncology, Ophthalmology,
and Pathology, as well as Tang Du Hospital in China, University of the Negevin, Israel, and the Instituto Neurologico C. Besta in Italy.
Biodegradable nanoparticles have shown recently promise as a method to deliver genes into cells. Their use for delivery avoids many of the problems associated with viral gene delivery.
To demonstrate virus free delivery the first goal of the group was to develop a nanoparticle that could efficiently carry DNA encoding a gene known as HSVTK into cells.
The HSVTK gene produces an enzyme that turns the compound ganciclovir --which by itself has no effect on cancer cells--into a compound that is toxic to actively dividing brain cancer cells.
A number of polymer structures were tested for their ability to deliver DNA into two rat glioma cell lines.
Among the many polymers tried, the one known as PBAE 447 was found to be the most efficient in delivering the HSVTK gene into the cultured rat glioma cells.
Furthermore when combined with ganciclovir, the HSVTK-encoding nanoparticles were 100%effective in killing both of the glioma cell lines grown in the laboratory.
Next, the gene therapy system was tested in live rats with brain gliomas. Because it is important that the nanoparticles spread throughout the entire tumor,
they were infused into the rat gliomas using convection-enhanced delivery (CED). The method involves injection into the tumor and the application of a pressure gradient,
which efficiently disperses the nanoparticles throughout the tumors. To test the tumor-killing ability of the system,
the tumor-bearing rats were given systemic administration of ganciclovir for two days, then CED was used to infuse the HSVTK-encoding nanoparticles into the rat gliomas,
and systemic ganciclovir treatment continued for eight more days. The treatment resulted in shrinkage of the tumors
and a significant increase in survival when compared with control glioma-bearing animals that did not receive the combination treatment."
"The results provide the first demonstration of a successful non-viral nanomedicine method for HSVTK/ganciclovir treatment of brain cancer,"stated Green."
"Next steps will include enhancing the efficiency of this nanoparticle delivery system and evaluating the technology in additional brain cancer animal models."
"In the future, the investigators envision that doctors would administer this therapy during the surgery commonly used to treat glioma in humans.
They are interested also in testing the ability to deliver other cancer-killing genes and whether the nanoparticles could be administered successfully systemically
--which could broaden the use of the therapy for a wide range of solid tumors and systemic cancers s
#Ultrasound accelerates skin healing, especially for diabetics and the elderly Researchers from the University of Sheffield's Department of Biomedical science discovered the ultrasound transmits a vibration through the skin
and wakes up cells in wounds helping to stimulate and accelerate the healing process. More than 200,000 patients in the UK suffer with chronic wounds every year at a cost of over £3. 1 billion to the NHS.
The ultrasound treatment, which also reduces the chance of wounds getting infected, is particularly effective
when treating diabetics and the elderly. There are 11 million over-65s three million diabetics, and 10 million smokers in the UK--all of whom are likely to suffer problems with healing wounds.
A quarter of diabetics suffer from skin ulcers, particularly foot ulcers, due to the loss of sensation and circulation in the legs.
Lead author of the study Dr Mark Bass, from the University's Centre for Membrane Interactions and Dynamics (CMIAD), said:"
"Skin ulcers are excruciatingly painful for patients and in many cases can only be resolved by amputation of the limb."
"Using ultrasound wakes up the cells and stimulates a normal healing process. Because it is just speeding up the normal processes,
the treatment doesn't carry the risk of side effects that are associated often with drug treatments."
"Arraydr Bass added:""Now that we have proven the effectiveness of ultrasound we need to explore the signal further.
We have found that the ultrasound signal we currently use is effective, but it is possible that by refining the treatment we could improve the effects even further."
"Because ultrasound is relatively risk free we could expect to see it in broad clinical use within three or four years. s
#New cell division mechanism discovered Canadian and British researchers have discovered that chromosomes play an active role in animal cell division.
This occurs at a precise stage--cytokinesis--when the cell splits into two new daughter cells.
It was observed by a team of researchers including Gilles Hickson, an assistant professor at the University of Montreal's Department of Pathology and Cell biology and researcher at the CHU Sainte-Justine Research Centre, his assistant Silvana Jananji, in collaboration with Nelio
Rodrigues, a Phd student, and Sergey Lekomtsev, a postdoc, working in the group led by Buzz Baum of the MRC Laboratory for Molecular Cell biology at University college London.
Their findings were published in Nature. Cell division is fundamental to all life forms: the human body develops from a single cell that divides billions of times to generate all tissue types,
and some of these cells continue to divide billions of times every day throughout life. For the moment, however, the molecular mechanisms involved are understood incompletely,
and it was unknown until now that chromosomes could play an active role at this step in cytokinesis.
Flawless division In animal cells, division involves mitosis, the separation of chromosomes followed by splitting of the cell into two new daughter cells by cytokinesis."
"Division is a complex and robust process that is generally performed flawlessly, but when an error occurs in DNA separation or during cytokinesis,
it can be a source for triggering cancer, for example,"said Hickson. It is well known that microscopic cable-like structures,
called microtubules, were involved in pulling chromosomes to opposite poles of the cell during the division process."
"At this time, microtubules physically separate the chromosomes via their central kinetochores while other microtubules signal to the cortex of the cell where its equator is, i e.,
, where division will take place, "Hickson explained. Furthermore until now, it was believed that the chromosomes only played a passive role:
that they were pulled by the microtubules and didn't affect cytokinesis, but this is not the case.
Chromosomes'active role Initially working with the cells of fruit flies using powerful genetic tools and sophisticated microscopy,
the research team discovered that chromosomes emit signals that influence the cortex of the cell to reinforce microtubule action.
One of the key signals involved that the researchers identified acts via an enzyme complex--a phosphatase known as Sds22-PP1
--which is found at the kinetochores. They also demonstrated that this signaling pathway acts in human cells."
"Such evolutionary conservation from flies to humans is expected for processes as fundamental as cell division, "he explained.
This is what makes fruit flies such a powerful system for helping us to understand human biology.""When chromosomes are segregated,
they approach the membrane at the poles of the cell, and thanks to this enzyme's actions, this contributes to the softening of the polar membrane,
facilitating the elongation of the cell and the ensuing division that occurs at the equator."
and to certain diseases,"said Hickson, who has devoted the last 15 years of his research life to cell biology.
In fact, all cancers are unchecked characterised by cell division, and the underpinning processes are potential targets for therapeutic interventions that prevent cancer onset and spread."
"But before we get there, we must continue to expand our knowledge about the basic processes
and signals involved in normal cell division to understand how they can go awry, or how they can be exploited..
Ultimately, this could help the rational design of more specific therapies to inhibit the division of cancer cells,
#Lynchpin molecule for the spread of cancer found Cancer is a disease of cell growth,
but most tumors only become lethal once they metastasize or spread from their first location to sites throughout the body.
For the first time, researchers at Thomas Jefferson University in Philadelphia report a single molecule that appears to be the central regulator driving metastasis in prostate cancer.
The study, published online July 13th in Cancer cell, offers a target for the development of a drug that could prevent metastasis in prostate cancer,
and possibly other cancers as well.""Finding a way to halt or prevent cancer metastasis has proven elusive.
We discovered that a molecule called DNA-PKCS could give us a means of knocking out major pathways that control metastasis before it begins,
"says Karen Knudsen, Ph d.,Director of the Sidney Kimmel Cancer Center at Thomas Jefferson University, the Hilary Koprowski Professor and Chair of Cancer Biology, Professor of Urology, Radiation Oncology,
and Medical Oncology at Jefferson. Metastasis is thought of as the last stage of cancer. The tumor undergoes a number of changes to its DNA--mutations--that make the cells more mobile
able to enter the bloodstream, and then also sticky enough to anchor down in a new location,
such as the bone, the lungs, the liver or other organs, where new tumors start to grow.
Although these processes are characterized fairly well, there appeared to be many non-overlapping pathways that ultimately lead to these traits.
Now, Dr. Knudsen and colleagues have shown that one molecule appears to be central to many of the processes required for a cancer to spread.
That molecule is a DNA repair kinase called DNA-PKCS. The kinase rejoins broken or mutated DNA strands in a cancer cell,
In fact, previous studies had shown that DNA-PKCS was linked to treatment resistance in prostate cancer, in part because it would repair the usually lethal damage to tumors caused by radiation therapy and other treatments.
Importantly, Dr. Knudsen's work showed that DNA-PKCS has other, far-reaching roles in cancer.
The researchers showed that DNA-PKCS also appears act as a master regulator of signaling networks that turn on the entire program of metastatic processes.
which allows many cancer cell types to become mobile, as well as a number of other gene networks involved in other steps in the metastatic cascade, such as cell migration and invasion.
In addition to experiments in prostate cancer cell lines, Dr. Knudsen and colleagues also showed that in mice carrying human models of prostate cancer,
And in mice with aggressive human tumors, an inhibitor of DNA-PKCS reduced overall tumor burden in metastatic sites.
In a final analysis that demonstrated the importance of DNA-PKCS in human disease the researchers analyzed 232 samples from prostate cancer patients for the amount of DNA-PKCS those cells contained
and compared those levels to the patients'medical records. They saw that a spike in the kinase levels was a strong predictor of developing metastases and poor outcomes in prostate cancer.
They also showed that DNA-PKCS was much more active in human samples of castrate-resistant prostate cancer, an aggressive and treatment-resistant form of the disease."
"These results strongly suggest that DNA-PKCS is a master regulator of the pathways and signals that lead to the development of metastases in prostate cancer,
and that high levels of DNA-PKCS could predict which early stage tumors may go on to metastasize,
"says Dr. Knudsen.""The finding that DNA-PKCS is a likely driver of lethal disease states was unexpected,
and the discovery was made possible by key collaborations across academia and industry,"explains Dr. Knudsen.
in addition to leaders of the Sidney Kimmel Cancer Center's Prostate Program, included the laboratories of Felix Feng (University of Michigan), Scott Tomlins (University of Michigan), Owen Witte (UCLA),
Cory Abate-Shen (Columbia University), Nima Sharifi (Cleveland Clinic) and Jeffrey Karnes (Mayo Clinic), and contributions from Genomedx.
"We are enthusiastic about the next step of clinical assessment for testing DNA-PKCS inhibitors in the clinic.
A new trial will commence shortly using the Celgene CC-115 DNA-PKCS inhibitor. This new trial will be for patients advancing on standard of care therapies,
and will be available at multiple centers connected through the Prostate Cancer Clinical Trials Consortium, of which we are explained a member
Dr. Knudsen.""Although the pathway to drug approval can take many years, this new trial will provide some insight into the effect of DNAP-PKCS inhibitors as anti-tumor agents.
In parallel, using this kinase as a marker of severe disease may also help identify patients whose tumors will develop into aggressive metastatic disease,
so that we can treat them with more aggressive therapy earlier, "says Dr. Knudsen.""Given the role of DNA-PKCS in DNA repair as well as control of tumor metastasis,
there will be challenges in clinical implementation, but this discovery unveils new opportunities for preventing or treating advanced disease
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