which could make it easier to pinpoint the causes of cancer. In many cases, genetic mutations that cause cancer involve chemical changes to individual building blocks of DNAREATING DNA ADDUCTS."
"Natural products can be a source of effective cancer drugs, and several are being used for treating a variety of cancers,
"Gavin Robertson says.""Over 60 percent of anticancer agents are derived from plants, animals, marine sources, or microorganisms.
And it impossible to determine the exact location where a building block in the genetic code has been altered into an adduct.
a professor of food and nutrition toxicology at ETH Zurich, has succeeded for the first time in amplifying gene samples containing DNA ADDUCTS
it may therefore be possible to expand DNA sequencing from the four basic DNA building blocks to include adducts. he scientific community would have an important tool for making a detailed analysis of the molecular mechanisms involved in the initiation of cancer
#Donor tissue for joint repair stays fresh for 60 days Currently doctors have to throw away more than 80 percent of donated tissue used for joint replacements
a professor of orthopedic surgery at the University of Missouri School of medicine. he benefit to patients is that more graft material will be available
This will allow us as surgeons to provide a more natural joint repair option for our patients.
The technology, called the Missouri Osteochondral Allograft Preservation System (MOPS), more than doubles the storage life of bone
and cartilage grafts from organ donors compared to the current preservation method used by tissue banks.
donated tissues are stored within a medical-grade refrigeration unit in sealed bags filled with a standard preservation solution.
says study coauthor James Cook, director of the Comparative Orthopedic Laboratory and the Missouri Orthopedic Institute Division of Research. ith the traditional preservation approach,
we only have about 28 days after obtaining the grafts from organ donors before the tissues are no longer useful for implantation into patients. ost of this 28-day window of time is used for testing the tissues to ensure they are safe for use.
schedule surgery and get the graft to the surgeon for implantation. METAL IMPLANTS VS. TISSUE GRAFTS Stannard says that patients with metal and plastic implants often are forced to give up many of the activities they previously enjoyed
in order to extend the life of their new mechanical joints . or patients with joint problems caused by degenerative conditions,
metal and plastic implants are still a very good option, Stannard adds. hen the end of a bone that forms a joint is destroyed over time,
the damage is often too extensive to use tissue grafts. owever, for patients who experience trauma to a joint that was otherwise healthy before the injury,
previous activity levels needn be altered drastically if we can replace the damaged area with living tissue.
However, the method of preserving the grafts themselves has limited the amounts of quality donor tissue available to surgeons. 100%USABLE AT 60 DAYS Additionally, because of testing requirements and logistics,
#Bed nets can#t stop new#super mosquito#Bed nets treated with insecticide aren enough to stop a new uper mosquito?
Anopheles gambiae, a major malaria vector, is isolated interbreeding with pockets of another malaria mosquito, A. coluzzii. Entomologists initially considered them as the
and S formsof Anopheles gambiaeut now recognize them as separate species. t uperwith respect to its ability to survive exposure to the insecticides on treated bed nets,
says medical entomologist Gregory Lanzaro, professor in the pathology, microbiology and immunology department at University of California,
in this case a breakdown in the reproductive isolation that separates them, Lanzaro says. hat we provide in this new paper is an example of one unusual mechanism that has promoted the rapid evolution of insecticide resistance in one of the major malaria mosquito species
. The insecticide resistance came as no surprise, Lanzaro says. rowing resistance has been observed for some time. Recently it has reached a level at some localities in Africa where it is resulting in the failure of the nets to provide meaningful control,
Insecticide-treated nets can be credited with saving many thousands probably tens of thousands of lives, in Mali alone, Lanzaro says.
The World health organization World Malaria Report indicates that deaths from malaria worldwide have decreased by 47 percent since 2000.
Much of that is attributed to the insecticide-treated bed nets. However, it was just a matter of time for insecticide resistance to emerge.
Now there n urgent need to develop new and effective malaria vector control strategies, Lanzaro says.
A number of new strategies are in development, including new insecticides, biological agentsncluding mosquito-killing bacteria and fungind genetic manipulation of mosquitoes aimed at either killing them
or altering their ability to transmit the malaria parasite. Other researchers from UC Davis and from the University of Bamako in Mali are coauthors of the study The National institutes of health funded the research
#High-res MRI links cerebellum to bipolar disorder A different type of MRI has given researchers an unprecedented look at previously unrecognized differences in the brains of people with bipolar disorder, a new study reports.
Specifically, the findings reveal differences in the white matter of patientsbrains and in the cerebellum, an area of the brain not previously linked with the disorder.
The cerebellar differences were not present in patients taking lithium, the most commonly used treatment for bipolar disorder.
A NEW PICTURE his imaging technique appears to be sensitive to things that just have not been imaged effectively before
professor of psychiatry at University of Iowa. o it really providing a new picture and new insight into the composition and function of the brain in bipolar disease.
Despite being relatively commonipolar disorder affects about one percent of the populationcientists don have a good understanding of what causes bipolar disorder,
Researchers examined 15 patients with bipolar disorder and 25 control subjects matched for age and gender.
ELEVATED MRI SIGNAL Compared to the brains of people without bipolar disorder, the MRI signal was elevated in the cerebral white matter
and the cerebellar region of patients affected by bipolar disorder. The elevated signal may be due to either a reduction in ph or a reduction in glucose concentrationoth factors influenced by cell metabolism.
Previous research has suggested that abnormal cell metabolism may play a role in bipolar disorder. However, investigating metabolic abnormalities in the brain has been hindered by lack of a good imaging tools.
Available methods are slow low-resolution, and require researchers to identify the region of interest at the beginning of the study.
The study is the first time this MRI technique has been used to investigate a psychiatric disease. One reason researchers didn know that the cerebellum might be important in bipolar disorder,
is because no one chose to look there, says Casey Johnson, postdoctoral researcher and first author on the study that is published in the journal Molecular Psychiatry. ur study was essentially exploratory.
We didn know what we would find. The majority of bipolar disorder research has found differences in the frontal region of the brain.
We found focal differences in the cerebellum, which is a region that hasn really been highlighted in the bipolar literature before."
and go to a doctor, aggregation already has a stronghold in their brains, "says Lisa Lapidus,
and other diseases that involve neurotoxic aggregation. MRI probe detects Alzheimer's at earliest stage Spurred on by the finding,
the researchers conducted an extensive search of the scientific literature on bipolar disorder and began to find pieces of evidence that suggested that the cerebellum may function abnormally in bipolar disorder
and that lithium might potentially target the cerebellum and alter glucose levels in this brain region. ur paper,
The researchers hope that the new insights provided by the T1 rho imaging might help refine understanding of the abnormalities that underlie bipolar disease
While lithium can be an effective mood stabilizer for people with bipolar disorder, it causes numerous unpleasant side effects for patients. f lithium effect on the cerebellum is the key to its effectiveness as a mood stabilizer,
then a more targeted treatment that causes the same change in the cerebellum without affecting other systems might be a better treatment for patients with bipolar disorder,
Wemmie says. A philanthropic gift from University of Iowa alumnus Roger Koch, the National institutes of health, the Department of veterans affairs,
and the National Alliance for Research on Schizophrenia and Depression provided funding for the study.
Source: University of Iow g
#Could cell#backpacks#deliver inflammation drugs? Scientists have created ellular backpacksthat could carry therapeutic agents to the site of inflammation
and then release them. Inflammation is a normal way for the body to respond to injury or infection.
The swelling, heat, and even pain are the body trying to protect its soft tissue, remove offending objects, substances,
or microbes, and start healing. ASICALLY THE MAIN BENEFIT IS THAT YOU CAN DELIVER THE DRUG IN A MORE EFFECTIVE DOSE However,
or even tissue death. any diseases result in inflammation, says Samir Mitragotri, professor of chemical engineering at University of California, Santa barbara,
and director of the campus Center for Bioengineering. Whether inflammation is a byproduct of the disease
or the inflammation is the disease, it is a common indicator of a problem with the system. f we could target the common denominator,
whether the inflammation is coming from cancer or arthritis, we could deliver the drug there,
says Mitragotri, who specializes in targeted drug delivery. By taking advantage of natural body processes, researchers at UC Santa barbara and MIT have developed a method of targeting inflamed tissues
says grad student researcher Aaron Anselmo, lead author of a study in the current issue of the Journal of Controlled Release.
Once at the site, these monocytes transform into macrophages, cells that reside in the affected tissues to engulf
Working with the expertise of chemical engineering and materials science researchers at MIT, the researchers developed an approach based on ellular backpacks?
hold therapeutic agents that can be released at the site of the inflammation. These polymeric discs are coated on one side with a single layer of an antibody that can bind to receptors on the monocyte surface.
To prevent the cellular backpack from being engulfed and devoured by the very cell that is transporting it,
At the inflamed site, the particles would simultaneously degrade and release their drugs.""It is a good idea to get your levels checked on a yearly basis
you and your doctor can make a plan on how to reverse it through diet, supplements,
or other therapies,"says Adam Murphy. Low Vitamin d linked to aggressive prostate cancer The development of effective cellular backpacks has broad potential,
say the researchers. asically the main benefit is that you can deliver the drug in a more effective dose,
which often has a narrow therapeutic range: too little and the treatment is not effective, too much and it can be lethal.
Not only can targeted therapy ensure other body systems remain unaffected, Mitragotri explains, but it could also allow for higher doses of drug to the site,
which could decrease treatment time h
#Bad stuff would happen if your brain didn#t cycle A study with mice shows how the mammalian brain is able to maintain a constant state of up and downhile under anesthesia, during slow-wave sleep,
or even amid calm wakefulness. The findings suggest how the brain walks a healthy line between excitement
a bit like a car at a stoplight. t is very important to regulate that balance of excitation
a professor and chair of neuroscience at Brown University and senior author of the study. oo much excitation relative to inhibition you get a seizure,
Complicated process The researchers focused on five different types of cells in a particular area of the mouse cortex
Garrett Neske, a graduate student at Brown University and lead author of the study, induced up and down cycles in slices of tissue from the barrel cortex
such as its firing rate and the amounts of excitation and inhibition they received from other neurons.
and it calls for more comparative work to be done among cortical areas, Neske says. ou can just use one cortical region as the model for all inhibitory interneuron function.
#How lasers make metal super water repellent Scientists have used lasers to turn metals into extremely water repellent materials without the need for temporary coatings.
both of the University of Rochester Institute of Optics, describe a powerful and precise laser-patterning technique that creates an intricate pattern of micro
-and nanoscale structures to give the metals their new properties. This work builds on earlier research by the team in which they used a similar laser-patterning technique that turned metals black.
Guo says that with this technique, they can create multifunctional surfaces that are not only super-hydrophobic but also highly-absorbent optically.
Guo adds that one of the big advantages of his team process is that he structures created by our laser on the metals are intrinsically part of the material surface.
And it is these patterns that make the metals repel water. he material is so strongly water-repellent,
says Guo, a professor of optics. That whole process takes less than a second. MORE SLIPPERY THAN TEFLON The materials Guo has created are much more slippery than Teflon common hydrophobic material that often coats nonstick frying pans.
Unlike Guo laser-treated metals, the Teflon kitchen tools are not super-hydrophobic. The difference is that to make water to roll off a Teflon coated material,
You can make water roll off Guo metals by tilting them less than five degrees. As the water bounces off the super-hydrophobic surfaces
Guo and his team took ordinary dust from a vacuum cleaner and dumped it onto the treated surface.
but ultra-short laser pulses to change the surface of the metals. A femtosecond laser pulse lasts on the order of a quadrillionth of a second
MULTIFUNCTIONAL METALS Guo is keen to stress that this same technique can give rise to multifunctional metals.
Metals are naturally excellent reflectors of light. That why they appear to have a shiny luster.
The combination of light-absorbing properties with making metals water repellent could lead to more efficient solar absorbersolar absorbers that don rust
as well as studying how to expand this technique to other materials such as semiconductors or dielectrics, opening up the possibility of water repellent electronics.
The Bill & Melinda Gates Foundation and the United states Air force Office of Scientific research provided funding for the work p
#Hybrid crystals fuse semiconductors and metal Tomorrow's computers and electronics will require extremely small high-quality circuits.
Comprised of both a semiconductor and metal the material has a special superconducting property at very low temperatures.
The superconductor in this case is aluminium. Thomas Sand Jespersen an associate professor at the University of Copenhagen who helped create the material says it's a way to make a perfect transition between the nanowire and a superconductor.
Nanowires are extremely thin nanocrystal threads used in the development of new electronic components like transistors and solar cells.
Part of the challenge of working with nanowires is creating a good transition between these nanowires and an electrical contact to the outside world.
Up until now researchers have cultured nanowires and the contact separately. However with the new approach both the quality and the reproducibility of the contact have improved considerably.
The atoms sit in a perfectly ordered lattice in the nanowire crystal not only in the semiconductor and the metal but also in the transition between the two very different components which is significant in itself explains Peter Krogstrup an assistant professor who helped develop the contact.
Krogstrup says it is the ultimate limit to how perfect a transition one could imagine between a nanowire crystal and a contact.
He thinks it opens many opportunities to make new types of electronic components on the nanoscale to study the electrical properties with much greater precision than before In their publication in Nature Materials the research group has demonstrated this perfect contact
and its properties and has shown also that they can make a chip with billions of identical semiconductor-metal nanowire hybrids.
We think that this new approach could ultimately form the basis for future superconducting electronics says Jespersen.
Microsoft the Carlsberg Foundation and the Lundbeck Foundation supported the work r
#Shire Acquires NPS Pharma for $5. 2b Shire will acquire NPS Pharmaceuticals for about $5. 2 billion cash,
the companies said Sunday, in a deal that expands the buyer gastrointestinal (GI) disorders and rare-disease portfolios,
as well as its global footprint. Both companies'boards have approved the deal, which is expected to close during the first quarter of this yearubject to conditions that include the tender of a majority of the outstanding NPS Pharma shares,
and the receipt of Hart-Scott-Rodino clearance. The Shire-NPS deal comes less than two weeks before NPS faces a key decision from the FDAHETHER to approve its biologics license application (BLA) for Natpara
a parathyroid hormone (rhpth 1-84) that if approved would be the first bioengineered hormone replacement therapy for hypoparathyroidism (HPT.
The drug PDUFA target date for a decision is January 24. That date was delayed three months in October,
an injection drug indicated for long-term treatment of adults with short bowel syndrome (SBS) who need parenteral support.
Gattex, the first approved GLP-2 analog approved for treating SBS would complement Shire existing stable of drugs for gastrointestinal diseases."
"The acquisition of NPS Pharma is a significant step in advancing Shire's strategy to become a leading biotechnology company, Shire CEO Flemming Ornskov, M d,
. M p h.,said in a statement.""We look forward to accelerating the growth of the NPS Pharma portfolio based on our proven track record of maximizing value from acquired assets and commercial execution.
The NPS Pharma organization will be a welcome addition to Shire as we continue to help transform the lives of patients with rare diseases."
e believe that joining our two companies will drive value for shareholders and ensure we continue to transform the lives of patients with short bowel syndrome, hypoparathyroidism,
and autosomal dominant hypocalcemia worldwide. Gattex generated $67. 9 million in net sales during the first three quarters of 2014,
and a new indication for teduglutide, pediatric SBS. NPS Pharma is now conducting a global study for teduglutide in pediatric patients with SBS who are dependent on parenteral support.
NPS has licensed several of its products through partnerships with several biopharma giants. Amgen markets cinacalcet HCL as Sensipar in the U s. and as Mimpara in the EU;
Janssen Pharmaceuticals markets tapentadol as Nucynta in the U s.;and Kyowa hakko Kirin markets cinacalcet HCI as Regpara in Japan, Hong kong, Malaysia, Macau, Singapore, and Taiwan.
Shire said it anticipates synergies approximating 25-35%of the Street's consensus forecast of NPS Pharma's standalone future operating cost base from 2017 onward.
At $46 per share, the deal price reflects a 51%premium to NPS Pharma share price of $30. 47 on December 16, 2014,
when speculation about a Shire acquisition of NPS surfacedut only a 9. 8%premium from NPSCLOSING price Friday of $41. 91.
Shire plans to will finance the deal in part through a new $850 million fully underwritten short-term bank facility in addition to Shire's cash and cash equivalents and an existing $2. 1 billion five
-year revolving credit facility. Shire plans to refinance the short-term bank facility, it said, by issuing new debt
#Molecule that Destroys Apoptotic Cells also Repairs Damaged Axons Two new studies involving the University of Colorado Boulder and the University of Queensland (UQ) in Brisbane,
Australia, have identified a molecule that not only destroys inflammatory and apoptotic cells, but also has the ability to repair damaged nerve cells.
Known as the phosphatidylserine receptor, or PSR-1, the molecule can locate and clear out apoptotic cells that are preprogrammed to die as well as necrotic cells that have been injured
Ding Xue, Ph d.,a professor in the department of molecular, cellular, and developmental biology at CU-Boulder.
Apoptosis is a natural process that kills billions of cells in a typical human body each day. But it is the finding that the PSR-1 molecule also can help reconnect
and knit together broken axons that has caught the attention of both science teams.""I would call this an unexpected
"This is the first time a molecule involved in apoptosis has been found to have the ability to repair severed axons,
and we believe it has great therapeutic potential.""Dr. Xue is the lead author in a paper (lysine-rich motif in the phosphatidylserine receptorpsr-1 mediates recognition
and hopefully move toward solving injuries,"said Dr. Hilliard. In the future, neurosurgery may be combined with molecular biology to deliver positive clinical outcomes
and perhaps treat conditions like spinal cord or nerve injuries, he said. During programmed cell death,
apoptotic cells flag themselves for elimination by moving a specific cell membrane component known as phosphatidylserine (PS) from the inner membrane to the cell surface,
"While biomedical researchers have had some successes in repairing peripheral nerves and nerve clusters outside the brain and spinal cord in humans,
Such nerve damage can cause partial or total paralysis. Xue, who first identified the PSR-1 receptor in 2003,
"We are trying to understand how PSR-1 removes cells through apoptosis and necrosis, and they are trying to understand
if molecules involved in apoptosis also play a role in the neuroregeneration process, "said Dr. Xue.
According to Dr. Xue, C. elegans is an ideal organism to use in the hunt for new therapeutics to treat nerve damage because of its relatively small,
well-known genome and short life span of just a few days.""This makes drug screening much easier,
faster and less expensive than using a mouse model, for instance, "he explained.""The big finding is that we have a single receptor that does two different jobs,"noted Dr. Xue."
but we feel these findings offer promise in seeking new and effective therapeutics. c
#Small Molecule Successfully Targets Telomerase to Destroy Cancer cells Scientists at the University of Texas Southwestern Medical center report that they have targeted telomeres with a small molecule called 6-thiodg that takes advantage of the cell's biological clock to kill cancer cells
and shrink tumor growth. Jerry W. Shay, Ph d.,professor and vice chairman of cell biology at UT Southwestern,
and colleague, Woodring E. Wright, M d.,Ph d.,professor of cell biology and internal medicine, found that 6-thio-2'-deoxyguanosine could stop the growth of cancer cells in culture and decrease the growth of tumors in mice.
Drs. Shay and Wright are co-senior authors of the study nduction of Telomere Dysfunction Mediated by the Telomerase Substrate Precursor 6-Thio-2deoxyguanosineappearing in Cancer Discovery. reatment with 6-thio
-dg resulted in rapid cell death for the vast majority of the cancer cell lines tested,
whereas normal human fibroblasts and human colonic epithelial cells were unaffected largely, wrote the investigators. n A549 lung cancer cellased mouse xenograft studies,
6-thio-dg caused a decrease in the tumor growth rate superior to that observed with 6-thioguanine treatment.
In addition, 6-thio-dg increased telomere dysfunction in tumor cells in vivo. These results indicate that 6-thio-dg may provide a new telomere-addressed telomerase-dependent anticancer approach."
"We observed broad efficacy against a range of cancer cell lines with very low concentrations of 6-thiodg,
as well as tumor burden shrinkage in mice,"noted Dr. Shay, who is also associate director of the Harold C. Simmons Comprehensive Cancer Center.
Cancer cells are protected from apoptosis by telomerase, which ensures that telomeres do not shorten with every division.
Telomerase has therefore been the subject of intense research as a target for cancer therapy.
Drugs that successfully block its action have been developed, but these drugs have to be administered for long periods of time to successfully trigger cell death and shrink tumors,
leading to considerable toxicities. This outcome is partially because cells in any one tumor have chromosomes with different telomere lengths
and any one cell's telomeres must be shortened critically to induce death. 6-thiodg is used preferentially as a substrate by telomerase
and disrupts the normal way cells maintain telomere length. Because 6-thiodg is used not normally in telomeres,
Telomerase is an almost universal oncology target, yet there are few telomerase-directed therapies in human clinical trials,
researchers noted.""Using telomerase to incorporate toxic products into telomeres is remarkably encouraging at this point,
"said Dr. Wright. Importantly, unlike many other telomerase-inhibiting compounds, the researchers did not observe serious side effects in the blood,
"Since telomerase is expressed in almost all human cancers, this work represents a potentially innovative approach to targeting telomerase-expressing cancer cells with minimal side effects on normal cells,"continued Dr. Shay."
"We believe this small molecule will address an unmet cancer need in an underexplored area that will be rapidly applicable to the clinic
#Ultra-Fast Software Developed to Scan the Human genome Researchers at Nationwide Children's Hospital say they have developed an analysis pipeline that cuts the time it takes to search a person's genome for disease-causing variations from weeks to hours.
An article (hurchill: an ultra-fast, deterministic, highly scalable and balanced parallelization strategy for the discovery of human genetic variation in clinical and population-scale genomics appears in Genome Biology."
"It took around 13 years and $3 billion to sequence the first human genome,"notes Peter White, Ph d.,principal investigator and director of the biomedical genomics core at Nationwide Children's and the study's senior author."
"Now, even the smallest research groups can complete genomic sequencing in a matter of days.
However, once you've generated all that data, that's the point where many groups hit a wall.
After a genome is sequenced, scientists are left with billions of data points to analyze before any truly useful information can be gleaned for use in research and clinical settings."
"To overcome the challenges of analyzing that large amount of data, Dr. White and his team developed a computational pipeline called"Churchill."
"By using novel computational techniques, Churchill allows efficient analysis of a whole genome sample in as little as 90 minutes,
explains Dr. White.""Churchill fully automates the analytical process required to take raw sequence data through a series of complex and computationally intensive processes,
ultimately producing a list of genetic variants ready for clinical interpretation and tertiary analysis, "he continues."
without sacrificing data integrity, resulting in an analysis method that is 100 percent reproducible.""The output of Churchill (Genomenext has licensed its algorithm) was validated using National Institute of Standards and Technology (NIST) benchmarks.
In comparison with other computational pipelines, Churchill was shown to have the highest sensitivity at 99.7%;
%"At Nationwide Children's we have a strategic goal to introduce genomic medicine into multiple domains of pediatric research and healthcare.
Rapid diagnosis of monogenic disease can be critical in newborns, so our initial focus was to create an analysis pipeline that was extremely fast,
Churchill allows computationally efficient analysis of a high-depth whole genome sample in less than two hours,
000 Genomes raw sequence dataset in a week using cloud resources
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