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Petri dish-grown lens gives hope for new eye treatment

Petri dish-grown lens gives hope for new eye treatment | Amazing Science | Scoop.it

Pluripotent stem cells have the ability to become any cell in the human body including, skin, blood and brain matter. Once the stem cells have begun to differentiate, the challenge for researchers is to control the process and produce only the desired, specific cells.

Using a technology known as fluorescence activated cell sorting (FACS), Associate Professor Barberi and his team were able to identify the precise combination of protein markers expressed in the lens epithelium that enabled them to isolate those cells from the rest of the cultures. Most markers are common to more than one type of cell, making it challenging to determine the exact mix of markers unique to the desired cells.

Associate Professor Barberi said this breakthrough would eventually help cure visual impairment caused by congenital cataracts or severe damage to the lens from injury through lens transplants.

"The lens has, to some extent, the ability to heal well following surgical intervention. However, with congenital cataracts, the fault is wired into the DNA, so the lens will re-grow with the original impairment. This problem is particularly prevalent in developing countries," he said.

Combined with advances in producing pluripotent stem cells from fully-differentiated adult cells, the research will also progress treatments for eye diseases.

"In the future, we will be able to take adult skin cells, for example, and turn back the clock to produce stem cells. From there, using processes like we have developed for lens epithelium, we will be able to produce diseased cells - an invaluable asset for medical research," Associate Professor Barberi said.

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Scientists link excess blood sugar to cancer

Scientists link excess blood sugar to cancer | Amazing Science | Scoop.it

It is well known that obesity is a leading cause of diabetes, a disease where the body fails to control blood sugar levels. High blood sugar levels are characteristic in obesity and diabetes. What is less well known is that diabetes and obesity are also linked to an increase in cancer risk. That is, the diabetic population has up to double chances to suffer pancreatic or colon cancer among others, according to well sustained epidemiological studies. With obesity in British and Spanish children reaching 16%, the highest in Europe, this epidemic has major health implications. How obesity or diabetes increase cancer risk has been a major health issue. Scientists led by Dr. Custodia Garcia-Jimenez at the University Rey Juan Carlos in Madrid have uncovered a key mechanism that links obesity and diabetes with cancer: high sugar levels, which increase activity of a gene widely implicated in cancer progression. Dr Garcia Jimenez's laboratory was studying how cells in the intestine respond to sugars and signal to the pancreas to release insulin, the key hormone that controls blood sugar levels. Sugars in the intestine trigger cells to release a hormone called GIP that enhances insulin release by the pancreas. In a study published in Molecular Cell, Dr Garcia Jimenez's team showed that the ability of the intestinal cells to secrete GIP is controlled by a protein called β-catenin, and that the activity of β-catenin is strictly dependent on sugar levels. Increased activity of β-catenin is known to be a major factor in the development of many cancers and can make normal cells immortal, a key step in early stages of cancer progression. The study demonstrates that high (but not normal) sugar levels induce nuclear accumulation of β-catenin and leads to cell proliferation. The changes induced on β-catenin, the molecules involved and the diversity of cancer cells susceptible to these changes are identified.

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MIT: New technique pinpoints protein locations, helping scientists figure out their functions

MIT: New technique pinpoints protein locations, helping scientists figure out their functions | Amazing Science | Scoop.it

To get a clear picture of what’s happening inside a cell, scientists need to know the locations of thousands of proteins and other molecules. MIT chemists have now developed a technique that can tag all of the proteins in a particular region of a cell, allowing them to more accurately map those proteins.

“That’s a holy grail for biology — to be able to get spatially and temporally resolved molecular maps of living cells,” says Alice Ting, the Ellen Swallow Richards Associate Professor of Chemistry at MIT. “We’re still really far from that goal, but the overarching motivation is to get closer to that goal.”

Ting’s new method, developed with researchers from the Broad Institute and Harvard Medical School, combines the strengths of two existing techniques — microscopic imaging and mass spectrometry — to tag proteins in a specific cell location and generate a comprehensive list of all the proteins in that area. 

In a paper appearing in the Jan. 31 online edition of Science, Ting and colleagues used the new technique to identify nearly 500 proteins located in the mitochondrial matrix — the innermost compartment of the cellular organelle where energy is generated.

 

Using fluorescence or electron microscopy, scientists can determine protein locations with high resolution, but only a handful of a cell’s approximately 20,000 proteins can be imaged at once. “It’s a bandwidth problem,” Ting says. “You certainly couldn’t image all the proteins in the proteome at once in a single cell, because there’s no way to spectrally separate that many channels of information.”

With mass spectrometry, which uses ionization to detect the mass and chemical structure of a compound, scientists can analyze a cell’s entire complement of proteins in a single experiment. However, the process requires dissolving the cell membrane to release a cell’s contents, which jumbles all of the proteins together. By purifying the mixture and extracting specific organelles, it is then possible to figure out which proteins were in those organelles, but the process is messy and often unreliable. 

The new MIT approach tags proteins within living cells before mass spectrometry is done, allowing spatial information to be captured before the cell is broken apart. This information is then reconstructed during analysis by noting which proteins carry the location tag.

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Artificial pancreas a step closer for patients with type 1 diabetes

Artificial pancreas a step closer for patients with type 1 diabetes | Amazing Science | Scoop.it
Dual-hormone artificial pancreas is a step closer for patients with type 1 diabetes. Randomized trial shows improved glucose levels, lower risk of hypoglycemia.


It is challenging for patients with type 1 diabetes to control their glucose levels because tight glucose control increases the incidence of hypoglycemia (dangerously low glucose levels). Insulin pump treatment, which provides a continuous predetermined subcutaneous supply of insulin, is available, but hypoglycemia still occurs. 

 

"Hypoglycemia is feared by most patients and remains the most common adverse effect of insulin therapy," writes Ahmad Haidar, Institut de Recherches Cliniques de Montréal and McGill University, with coauthors.

The dual-hormone artificial pancreas delivers insulin and glucagon using infusion pumps based on continuous glucose sensor readings as guided by an intelligent dosing algorithm. The infusion pumps and the glucose sensors are already on the market, but the intelligent algorithm was developed by the researchers in Montreal.

 


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Novel Nanosized Magnets for Controlled and Targeted Release of Drugs

Novel Nanosized Magnets for Controlled and Targeted Release of Drugs | Amazing Science | Scoop.it

Certain drugs are toxic by nature. For example, anti-cancer drugs developed to kill diseased cells also harm healthy ones. To limit the side effects of chemotherapy, it would be a great step forward if it were possible to release a drug only in the affected area of the body. In the context of the National Research Programme "Smart Materials" (NRP 62) - a cooperation between the SNSF and the Commission for Technology and Innovation (CTI) - researchers of ETH Lausanne, the Adolphe Merkle Institute and the University Hospital of Geneva have discovered a method that might represent an important step towards the development of an intelligent drug of this kind. By combining their expert knowledge in the areas of material sciences, biological nanomaterials and medicine, they were able to prove the feasibility of using a nanovehicle to transport drugs and release them in a controlled manner.

 

This nanocontainer is a liposome, which takes the shape of a vesicle. It has a diameter of 100 to 200 nanometers and is 100 times smaller than a human cell. The membrane of the vesicle is composed of phospholipids and the inside of the vesicle offers room for the drug. On the surface of the liposome, specific molecules help to target malignant cells and to hide the nanocontainer from the immune system, which might otherwise consider it a foreign entity and seek to destroy it. Now the researchers only needed to discover a mechanism to open up the membrane at will.

 

This is exactly what the researchers succeeded in doing. How they did it? By integrating into the liposome membrane superparamagnetic iron oxide nanoparticles (SPION), which only become magnetic in the presence of an external magnetic field. Once they are in the field, the SPION heat up. The heat makes the membrane permeable and the drug is released.

 

Researchers proved the feasibility of such a nanovehicle by releasing in a controlled manner a coloured substance contained in the liposomes. "We can really talk of nanomedicine in this context because, by exploiting superparamagnetism, we are exploiting a quantum effect which only exists at the level of nanoparticles," explains Heinrich Hofmann of the Powder Technology Laboratory of EPFL. SPION are also an excellent contrast agent in magnetic resonance imaging (MRI). A simple MRI shows the location of the SPION and allows for the release of the drug once it has reached the targeted spot.

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Assembly of a three-dimensional multitype tissue structures using magnetic levitation

Assembly of a three-dimensional multitype tissue structures using magnetic levitation | Amazing Science | Scoop.it

A longstanding goal in biomedical research has been to create organotypic co-cultures that faithfully represent native tissue environments. There is presently great interest in representative culture models of the lung, which is a particularly challenging tissue to recreate in vitro. This study used magnetic levitation in conjunction with magnetic nanoparticles as a means of creating an organized 3D co-culture of the bronchiole that sequentially layers cells in a manner similar to native tissue architecture. The 3D co-culture model was assembled from four human cell types in the bronchiole: endothelial cells, smooth muscle cells, fibroblasts, and epithelial cells. This study represents the first effort to combine these particular cell types into an organized bronchiole co-culture. These cell layers were first cultured in 3D by magnetic levitation and then manipulated into contact with a custom-made magnetic pen, and again cultured for 48 h. Hematoxylin & eosin staining of the resulting co-culture showed four distinct layers within the 3D co-culture.

 

Immunohistochemistry confirmed the phenotype of each of the four cell types, and showed organized extracellular matrix formation, particularly with collagen type I. Positive stains for CD31, von Willebrand factor, smooth muscle α-actin, vimentin, and fibronectin demonstrate the maintenance of phenotype for endothelial cells, smooth muscle cells, and fibroblasts. Positive stains for mucin-5AC, cytokeratin, and E-cadherin after 7 days with and without 1% FBS showed that epithelial cells maintained phenotype and function. This study validates magnetic levitation as a method for the rapid creation of organized 3D co-cultures that maintain phenotype and induce extracellular matrix formation.

 

See also Nano3D: http://tinyurl.com/afttky3

 

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Polymer film that gradually releases DNA provides a safer way to vaccinate

Polymer film that gradually releases DNA provides a safer way to vaccinate | Amazing Science | Scoop.it
Polymer film that gradually releases DNA coding for viral proteins could offer a better alternative to traditional vaccines.

 

Vaccines usually consist of inactivated viruses that prompt the immune system to remember the invader and launch a strong defense if it later encounters the real thing. However, this approach can be too risky with certain viruses, including HIV.

In recent years, many scientists have been exploring DNA as a potential alternative vaccine. About 20 years ago, DNA coding for viral proteins was found to induce strong immune responses in rodents, but so far, tests in humans have failed to duplicate that success.

 

MIT researchers describe a new type of vaccine-delivery film that holds promise for improving the effectiveness of DNA vaccines. If such vaccines could be successfully delivered to humans, they could overcome not only the safety risks of using viruses to vaccinate against diseases such as HIV, but they would also be more stable, making it possible to ship and store them at room temperature.

This type of vaccine delivery would also eliminate the need to inject vaccines by syringe, says Darrell Irvine, an MIT professor of biological engineering and materials science and engineering. “You just apply the patch for a few minutes, take it off and it leaves behind these thin polymer films embedded in the skin,” he says.

 

The researchers can control how much DNA gets delivered by tuning the number of polymer layers. They can also control the rate of delivery by altering how hydrophobic (water-fearing) the film is. DNA injected on its own is usually broken down very quickly, before the immune system can generate a memory response. When the DNA is released over time, the immune system has more time to interact with it, boosting the vaccine’s effectiveness.

The polymer film also includes an adjuvant — a molecule that helps to boost the immune response. In this case, the adjuvant consists of strands of RNA that resemble viral RNA, which provokes inflammation and recruits immune cells to the area.

The ability to provoke inflammation is one of the key advantages of the new delivery system, says Michele Kutzler, an assistant professor at Drexel University College of Medicine. Other benefits include targeting the wealth of immune cells in the skin, the use of a biodegradable delivery material, and the possibility of pain-free vaccine delivery, she says.

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Scientists Discover Children’s Cells Living in Mothers’ Brains

Scientists Discover Children’s Cells Living in Mothers’ Brains | Amazing Science | Scoop.it

The connection between mother and child is ever deeper than thought.

 

What it is that fetal microchimeric cells do in the mother’s body is unclear, although there are some intriguing possibilities. For example, fetal microchimeric cells are similar to stem cells in that they are able to become a variety of different tissues and may aid in tissue repair. One research group investigating this possibility followed the activity of fetal microchimeric cells in a mother rat after the maternal heart wasinjured: they discovered that the fetal cells migrated to the maternal heart and differentiated into heart cells helping to repair the damage. In animal studies, microchimeric cells were found in maternal brains where they became nerve cells, suggesting they might be functionally integrated in the brain. It is possible that the same may true of such cells in the human brain.

 

These microchimeric cells may also influence the immune system. A fetal microchimeric cell from a pregnancy is recognized by the mother’s immune system partly as belonging to the mother, since the fetus is genetically half identical to the mother, but partly foreign, due to the father’s genetic contribution. This may “prime” the immune system to be alert for cells that are similar to the self, but with some genetic differences. Cancer cells which arise due to genetic mutations are just such cells, and there are studies which suggest that microchimeric cells may stimulate the immune system to stem the growth of tumors. Many more microchimeric cells are found in the blood of healthy women compared to those withbreast cancer, for example, suggesting that microchimeric cells can somehow prevent tumor formation. In other circumstances, the immune system turns against the self, causing significant damage. Microchimerism is more common in patients suffering from Multiple Sclerosis than in their healthy siblings, suggesting chimeric cells may have a detrimental role in this disease, perhaps by setting off an autoimmune attack.

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Reprogammed induced pluripotent stem cells are not rejected by immune system

Reprogammed induced pluripotent stem cells are not rejected by immune system | Amazing Science | Scoop.it
Researchers uncover more evidence that reprogrammed stem cells are not attacked by the immune system, suggesting they may one day serve as effective therapies.

 

Because iPSCs can be derived from a patient’s own tissues, researchers believed that transplantation into that patient should not provoke an immune response. But in 2011, Yang Xu’s team at the University of California, San Diego, called such assumptions into question when they provided evidence that iPSCs derived from mice were attacked and rejected by the immune system when implanted into genetically identical mice.

 

This prompted Ashleigh Boyd and colleagues at Boston University Medical School to try a similar experiment themselves. They differentiated mouse-derived iPSCs into three different cell lines with two different methods and assessed the immune response, both in vitro and after transplantation into genetically identical mice. They found no evidence that white blood cell count increased in vitro, nor of immune rejection in the transplant experiments.

The researchers concede that the discrepancy between their results and Xu’s findings may result from transplanting the cells into different parts of the body. Nevertheless, they wrote, “our data support the idea that differentiated cells generated from autologous iPSCs could be applied for cell replacement therapy without eliciting immune rejection.”

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Gene mutation causes overactive telomerase and immortalizes malignant melanoma

Gene mutation causes overactive telomerase and immortalizes malignant melanoma | Amazing Science | Scoop.it

About ten percent of all cases of malignant melanoma are familial cases. The genome of affected families tells scientists a lot about how the disease.

 

The genome of affected families tells scientists a lot about how the disease develops. Prof. Dr. Rajiv Kumar of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) together with Prof. Dr. Dirk Schadendorf from Essen University Hospital studied a family where 14 family members were affected by malignant melanoma. The scientists analyzed the genomes of family members and found an identical mutation in the gene for telomerase, an enzyme often called ‘immortality enzyme’, in all persons studied. Telomerase protects the ends of chromosomes from being lost in the process of cell division and, thus, prevents that the cell ages and dies. The inherited gene mutation leads to the formation of a binding site for protein factors in the controlling region of the telomerase gene, causing it to become overactive. As a result, mutated cells overproduce telomerase and hence become virtually immortal.

 

This spectacular finding of the family analysis prompted the scientists to also look for mutated telomerase genes in non-inherited (sporadic) melanoma, which is much more common than the familial variant. In most of the tissue samples of melanomas of all stages they found alterations in the telomerase gene switch, which the researchers clearly identified as typical consequences of sun exposure. Even though these mutations were not identical to those found in the melanoma family, they had the same effect: overactive telomerase.

 

“We don’t believe that the telomerase gene in melanoma is mutated by pure chance, but that it is a so-called driver mutation that drives carcinogenesis,” says Rajiv Kumar. This is also confirmed by the surprising incidence of this alteration: The telomerase gene is the most frequently mutated gene in melanoma. “This is something we hadn’t expected, because malignant melanoma has been genetically analyzed thoroughly. But this mutation always seems to have been overlooked,” says Kumar.

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Leprosy spreads by reprogramming nerve cells into migratory stem cells

Leprosy spreads by reprogramming nerve cells into migratory stem cells | Amazing Science | Scoop.it

The surprising modus operandi of a neglected tropical disease could lead to new stem cell therapies.

 

The bacterium that causes leprosy spreads through the body by converting nerve cells into stem cells with migratory properties, according to research published today in the journal Cell. The new findings could improve treatments for leprosy and other infectious diseases caused by bacteria, and help clinicians to diagnose them earlier. They may also provide a safe method for developing stem cell treatments for a wide variety of other conditions.

 

Mycobacterium leprae is a parasitic bacterium that can only survive inside host cells. It evades detection by the host's immune system by infecting Schwann cells, the glial cells which form the fatty myelin tissue that insulates peripheral nerves and helps them to conduct impulses. Infected cells remain healthy in the early stages of infection but, soon enough, their myelin begins to degenerate, leading to the nerve damage, loss of sensation and blistering skin sores that are characteristic of the disease. 

Anura Rambukkana of the MRC Centre for Regenerative Medicine at the University of Edinburgh and his colleagues isolated Schwann cells from adult mice, grew them in Petri dishes and infected them with M. leprae. They found that the bacterium gradually turns off the genes that give Schwann cells their characteristic properties, and then activates another set of genes that transforms them into something resembling neural crest stem cells, which are only present in the embryo, and which migrate from the developing nervous along various routes to form a wide variety of tissues, including muscle, bone, cartilage, and the Schwann cells and sensory neurons of the peripheral nerves.

 

This genetic reprogramming helps to disseminate the disease – infected cells revert to a stem cell-like state, then proliferate and convert into immature muscle cells or other cell types that migrate away from the initial infection site, carrying their bacterial load with them. By hiding out in the cells, the bacteria can spread through the body without triggering an immune response.

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UNC researchers use luminescent p16INK4a mice to track cancer and aging in real-time

UNC researchers use luminescent  p16INK4a mice to track cancer and aging in real-time | Amazing Science | Scoop.it

esearchers from the University of North Carolina Lineberger Comprehensive Cancer Center have developed a new method to visualize aging and tumor growth in mice using a gene closely linked to these processes.

 

Researchers have long known that the gene, p16INK4a (p16), plays a role in aging and cancer suppression by activating an important tumor defense mechanism called ‘cellular senescence’. The UNC team led by Norman Sharpless, MD, Wellcome Distinguished Professor of Cancer Research and Deputy Cancer Center Director, has developed a strain of mice that turns on a gene from fireflies when the normal p16 gene is activated.  In cells undergoing senescence, the p16 gene is switched on, activating the firefly gene and causing the affected tissue to glow.

 

Throughout the entire lifespan of these mice, the researchers followed p16 activation by simply tracking the brightness of each animal.    They found that old mice are brighter than young mice, and that sites of cancer formation become extremely bright, allowing for the early identification of developing cancers.

 

“With these mice, we can visualize in real-time the activation of cellular senescence, which prevents cancer but causes aging.  We can literally see the earliest molecular stages of cancer and aging in living mice.” said Sharpless.

 

The researchers envision immediate practical uses for these mice.  By providing a visual indication of the activation cellular senescence, the mice will allow researchers to test substances and exposures that promote cellular aging (“gerontogen testing”) in the same way that other mouse models currently allow toxicologists to identify cancer-causing substances (“carcinogen testing”).  Moreover, these mice are already being used by scientists at UNC and other institutions to identify early cancer development and the response of tumors to anti-cancer treatments.

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Not an easy task: Finding cancer-specific genomics fingerprints

Not an easy task: Finding cancer-specific genomics fingerprints | Amazing Science | Scoop.it

Researchers from the Wellcome Trust Sanger Institute's cancer genome project have developed a computer model to identify the fingerprints of DNA-damaging processes that drive cancer development. Armed with these signatures, scientists will be able to search for the chemicals, biological pathways and environmental agents responsible.

 

"For a long time we have known that mutational signatures exist in cancer," says Dr Peter Campbell, Head of the cancer genome project and co-senior author of the paper. "For example UV light and tobacco smoke both produce very specific signatures in a person's genome. Using our computational framework, we expect to uncover and identify further mutational signatures that are diagnostic for specific DNA-damaging processes, shedding greater light on how cancer develops."

 

The computer model will help to overcome a fundamental problem in studying cancer genomes: that the DNA contains not only the mutations that have contributed to cancer development, but also an entire lifetime's worth of other mutations that have also been acquired. These mutations are layered on top of each other and trying to unpick the individual mutations, when they appeared, and the processes that caused them is a daunting task.

 

"The problem we have solved can be compared to the well-known cocktail party problem," explains Ludmil Alexandrov, first author of the paper from Sanger Institute. "At a party there are lots of people talking simultaneously and, if you place microphones all over the room, each one will record a mixture of all the conversations. To understand what is going on you need to be able to separate out the individual discussions. The same is true in cancer genomics. We have catalogues of mutations from cancer genomes and each catalogue contains the signatures of all the mutational processes that have acted on that patient's genome since birth. Our model allows us to identify the signatures produced by different mutation-causing processes within these catalogues."


To identify individual sets of mutations produced by a particular DNA-damaging agent, the cancer genome project at the Sanger Institute simulated cancer genomes and developed a technique to search for these mutational signatures. This approach proved to be very successful. The research team then explored the genomes of 21 breast cancer patients and identified five mutational signatures of cancer-causing processes in the real world.

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UCI team target p53 for treating wide spectrum of cancers

UCI team target p53 for treating wide spectrum of cancers | Amazing Science | Scoop.it

UC Irvine biologists, chemists and computer scientists have identified an elusive pocket on the surface of the p53 protein that can be targeted by cancer-fighting drugs. The finding heralds a new treatment approach, as mutant forms of this protein are implicated in nearly 40 percent of diagnosed cases of cancer, which kills more than half a million Americans each year.

 

In an open-source study published online this week in Nature Communications, the UC Irvine researchers describe how they employed a computational method to capture the various shapes of the p53 protein. In its regular form, p53 helps repair damaged DNA in cells or triggers cell death if the damage is too great; it has been called the “guardian of the genome.”

Mutant p53, however, does not function properly, allowing the cancer cells it normally would target to slip through control mechanisms and proliferate. For this reason, the protein is a key target of research on cancer therapeutics.

Within cells, p53 proteins undulate constantly, much like a seaweed bed in the ocean, making binding sites for potential drug compounds difficult to locate. But through a computational method called molecular dynamics, the UC Irvine team created a computer simulation of these physical movements and identified an elusive binding pocket that’s open only 5 percent of the time.

 

After using a computer to screen a library of 2,298 small molecules, the researchers selected the 45 most promising to undergo biological assays. Among these 45 compounds, they found one, called stictic acid, that fits into the protein pocket and triggers tumor-suppressing abilities in mutant p53s.

While stictic acid cannot be developed into a viable drug, noted study co-leader Peter Kaiser, professor of biological chemistry, the work suggests that a comprehensive screening of small molecules with similar traits may uncover a usable compound that binds to this specific p53 pocket.

 

“The discovery and pharmaceutical development of such a compound could have a profound impact on cancer treatments,” Kaiser said. “Instead of focusing on a specific form of the disease, oncologists could treat a wide spectrum of cancers, including those of the lung and breast.” He added that there is currently one group of experimental drugs – called Nutlins – that stop p53 degradation, but they don’t target protein mutations as would a drug binding to the newly discovered pocket.

 

The results are the culmination of years of labor by researchers with UC Irvine’s Institute for Genomics & Bioinformatics and the Chao Family Comprehensive Cancer Center.

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Diamond defects shrink MRI to nanoscale

Diamond defects shrink MRI to  nanoscale | Amazing Science | Scoop.it
Technique could be sensitive enough to detect structure of a single protein.

 

Diamond-based quantum devices can now make nuclear magnetic resonance measurements on the molecular scale. Work by two independent groups will make it easier to find out the structure of single biological molecules such as proteins without destroying or freezing them.

 

Nuclear magnetic resonance (NMR) and its close cousin magnetic resonance imaging (MRI) give information about a sample’s structure by detecting the weak magnetic forces in certain atomic nuclei, such as hydrogen. They work by detecting how molecules collectively resonate — like guitar strings that vibrate together — with electromagnetic waves of specific wavelengths. The techniques provide information about the structure of samples without damaging them — which is particularly important if the sample is a human body.

 

But to some researchers, whole bodies are less interesting than the molecules that they are made up of. “I want to push NMR and MRI to the molecular level,” says Friedemann Reinhard, a physicist at the University of Stuttgart in Germany. His team is one of two that have used NMR to detect hydrogen atoms in samples measuring just a few nanometers across.

 

Probing single molecules a few nanometres wide has been a major frustration in NMR. The detectors need to be a similar size to the sample, and the magnetic coils usually used cannot easily be made smaller than a few micrometers.


NMR and MRI measurements on the nanoscale have been done using powerful nanomagnets in a technique called magnetic resonance force microscopy — but that only worked with very cold samples.

 

Rugar and Reinhard took a different approach. Both teams made diamonds with defects in their crystal structure — a single nitrogen atom next to a missing carbon atom, a few nanometres below the surface. This gives the diamond a red fluorescent glow, which can be bright or dull depending on which way the nitrogen’s electrons are spinning.


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Inhibiting NLK in cancers with mutated PTEN could turn the cancer's strength against it

Inhibiting NLK in cancers with mutated PTEN could turn the cancer's strength against it | Amazing Science | Scoop.it

A mutation that allows cells to grow out of control could also provide a new way to target and destroy cancer cells. This potential Achilles’ heel comes from a mutation in a gene called PTEN, which is found in a wide range of cancers.

 

PTEN is one of many tumor suppressor genes that we have to prevent our cells from growing out of control. If the PTEN gene stops working because of a mutation, it can cause tumours to develop – indeed many tumors have a mutated form of PTEN. However when a door closes, a window opens: the PTEN mutation helps the tumor to grow, but it could also mark it out as a target.

 

Researchers from the Institute of Cancer Research, London, found that switching off another gene known as NLK (Nemo-like kinase) killed tumor cells that had the PTEN mutation. This makes NLK a good target for drug developers to create a new cancer treatment.


Initially, the researchers took samples of tumor cells with and without the mutation, and switched off genes for important proteins that are used for regulating lots of processes in the cell. To do this they used small interfering RNA (or siRNA) which interfere with the processes of specific genes. These siRNAs block the chain of events that allow a gene to produce a protein, effectively switching it off. By switching off 779 genes individually, they could look for ones where cells with the PTEN mutation died and cells without the mutation survived.

 

This is how the researchers discovered the powerful effect of switching off the NLK gene. They are not certain how this works but it appears to protect a protein called FOXO1 that can act as a backup tumor suppressor and cause the cancer cell to die. When PTEN is mutated, the FOXO1 protein becomes vulnerable to a process called phosphorylation, which means it is ejected from the cell nucleus and destroyed. NLK is one of the proteins that phosphorylates FOXO1 and so by switching off the NLK gene, FOXO1 is able to do its job.


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Engineered immune cells strongly resist HIV infection

Engineered immune cells strongly resist HIV infection | Amazing Science | Scoop.it

One of the big challenges in treating AIDS is that the virus is notorious for mutating, so patients must be treated with a cocktail of drugs — known as highly active antiretroviral therapy or HAART — which hit it at various stages of the replication process. The researchers were able to get around that problem with a new, multi-pronged genetic attack that blocks HIV on several fronts. Essentially, they hope to mimic HAART through genetic manipulation.

The technique hinges on the fact that the virus typically enters T cells by latching onto one of two surface proteins known as CCR5 and CXCR4.

 

Some of the latest drugs now used in treatment work by interfering with these receptors’ activity. A small number of people carry a mutation in CCR5 that makes them naturally resistant to HIV. One AIDS patient with leukemia, now famously known as the Berlin patient, was cured of HIV when he received a bone marrow transplant from a donor who had the resistant CCR5 gene.

 

Scientists at Sangamo BioSciences in Richmond, Calif., have developed a technique using a protein that recognizes and binds to the CCR5 receptor gene, genetically modifying it to mimic the naturally resistant version. The technique uses a zinc finger nuclease, a protein that can break up pieces of DNA, to effectively inactivate the receptor gene. The company is now testing its CCR5-resistant genes in phase-1 and -2 trials with AIDS patients at the University of Pennsylvania.

 

The Stanford scientists used a similar approach but with an added twist. They used the same nuclease to zero in on an undamaged section of the CCR5 receptor’s DNA. They created a break in the sequence and, in a feat of genetic editing, pasted in three genes known to confer resistance to HIV, Porteus said. This technique of placing several useful genes at a particular site is known as “stacking.”

 

Incorporating the three resistant genes helped shield the cells from HIV entry via both the CCR5 and CXCR4 receptors. The disabling of the CCR5 gene by the nuclease, as well as the addition of the anti-HIV genes, created multiple layers of protection.

 

Blocking HIV infection through both the CCR5 and CXCR4 receptors is important, Porteus said, as it hasn’t been achieved before by genome editing. To test the T cells’ protective abilities, the scientists created versions in which they inserted one, two and all three of the genes and then exposed the T cells to HIV.

 

Though the T cells with the single- and double-gene modifications were somewhat protected against an onslaught of HIV, the triplets were by far the most resistant to infection. These triplet cells had more than 1,200-fold protection against HIV carrying the CCR5 receptor and more than 1,700-fold protection against those with the CXCR4 receptor, the researchers reported. The T cells that hadn’t been altered succumbed to infection with 25 days.

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RNA Fragments in Exosomes May Yield Rapid, Accurate Cancer Diagnosis

RNA Fragments in Exosomes May Yield Rapid, Accurate Cancer Diagnosis | Amazing Science | Scoop.it

A new method to noninvasively diagnose cancer and monitor its progression could eliminate the need for painful and sometimes life-threatening biopsies. Fragments of RNA that cells eject in fatty droplets may point the way to a new era of cancer diagnosis, potentially eliminating the need for invasive tests in certain cases.

 

Cancer tumor cells shed microvesicles containing proteins and RNA fragments, called exosomes, into cerebral spinal fluid, blood, and urine. Within these exosomes is genetic information that can be analyzed to determine the cancer’s molecular composition and state of progression. Researchers at Massachusetts General Hospital discovered that exosomes preserve the genetic information of their parent cells in 2008, however exosomes have not seen widespread clinical testing as a means of cancer diagnosis until now.

 

“We have never really been able to detect the genetic components of a tumor by blood or spinal fluid,” says Harvard University neurologist Fred Hochberg. “This is really a new strategy.” He says exosome diagnostic tests could potentially detect and monitor the progression of a wide variety of cancers. He is one of the lead researchers in a multicenter clinical study using new exosomal diagnostic tests developed by New York City-based Exosome Diagnostics to identify a genetic mutation found exclusively in glioma, the most common form of brain cancer.

 

When treating other forms of cancer, surgeons are able to biopsy tumors to diagnose and monitor the state of the disease. For brain cancers like glioma, however, multiple biopsies can be life threatening. Bob Carter, head of neurosurgery at the University of California, San Diego, says well-preserved RNA in blood and spinal fluid enables researchers to test and monitor for these genetic changes noninvasively.

 

He says study researchers separate exosomes from bio-fluids with a diagnostic kit and then extract the relevant genomic information. Once the specific cancer mutation is identified, clinicians will periodically draw additional bio-fluids to monitor the mutation levels to determine whether a patient is responding to therapy.  

 

Whereas Magnetic Resonance Imaging (MRI) is a useful tool, tumors only show up on imaging scans once they are at least one millimeter in diameter and comprise about 100,000 tumor cells. By that time, it may be too late for an early intervention. On the flip side, MRIs can also yield false positives. Hochberg says individuals who have been treated with conventional radiation therapy often have benign residual tissue from dying tumor cells that have been killed by the treatment but which the body has not yet eliminated. This tissue is often mistaken for tumor growth on a MRI scan. “You would identify to the patient that the drug is not working when in reality it is doing well,” Hochberg says. “On the other hand, having an easily accessible biomarker for glioma would give you a clear response.”

 

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Saliva Test for Red Hair Gene Developed

Saliva Test for Red Hair Gene Developed | Amazing Science | Scoop.it

A British ancestry company, BritainsDNA, is now offering parents the chance to see if their children might inherit the so-called "ginger gene". The test will scan each parent's DNA for signs of the so-called MC1R gene that causes redheadedness.

 

"Through a simple saliva test to determine deep ancestry, we can … identify whether an individual is a carrier of any of the three common redhead variants in the gene MC1R," said Dr. Jim Wilson, chief scientist at BritainsDNA, as quoted in the Huffington Post.

 

The gene for red hair is recessive, so a person needs two copies of that gene for it to show up or be expressed. That means even if both parents carry the gene, just one in four of their children are likely to turn out to be a redhead. As a result, families that have no redheads for decades can suddenly discover a carrottop in their midst.

 

"Families can carry a variant for generations, and when one carrier has children with another carrier, a redheaded baby can appear seemingly out of nowhere." Wilson said, as quoted in the Daily Mail.

 

Though there's no scientific evidence that redheads deserve their reputation for having fiery temperaments, some recent reports suggest having red hair is associated with a number of health issues. A study from the journal Nature found that the pigment pheomelanin, which is responsible for red hair, may also make redheads even more susceptible to melanoma than fair-skinned blondes, according to the Los Angeles Times.

 

And a widely reported study from the Journal of the American Dentistry Association found that redheads are more sensitive to pain and require extra anesthesia during surgery, according to ABC News.

 

But there may be some advantages to having red hair, too, EverydayHealth.com reports. The pale skin that redheads usually have is more efficient at soaking up sunlight — and sunlight is required for the body to manufacture vitamin D, an essential nutrient.

 

Worldwide, red hair is quite rare, and just over 0.5 percent, or one in 200 people, are redheads — this amounts to almost 40 million people, the Daily Mail reports.

 

In Ireland, an estimated 10 percent of the population has red hair, though about 40 percent of the Irish carry the recessive gene. In Scotland and England, 13 percent and 6 percent, respectively, are redheaded, according to the Daily Mail.

 

The DNA test will be offered by BritainsDNA at a genealogy and ancestry exhibition named Who Do You Think You Are, associated with the popular NBC television show and scheduled to be held in London next month.

 

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The science behind 'beatboxing'

The science behind 'beatboxing' | Amazing Science | Scoop.it

Using the mouth, lips, tongue and voice to generate sounds that one might never expect to come from the human body is the specialty of the artists known as beatboxers. Now scientists have used scanners to peer into a beatboxer as he performed his craft to reveal the secrets of this mysterious art.

 

The human voice has long been used to generate percussion effects in many cultures, including North American scat singing, Celtic lilting and diddling, and Chinese kouji performances. In southern Indian classical music, konnakol is the percussive speech of the solkattu rhythmic form.  In contemporary pop music, the relatively young vocal art form of beatboxing is an element of hip-hop culture.

 

Until now, the phonetics of these percussion effects were not examined in detail. For instance, it was unknown to what extent beatboxers produced sounds already used within human language.


Via Ashish Umre
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Dominant-negative p53 mutation hinders cancer treatment response

Dominant-negative p53 mutation hinders cancer treatment response | Amazing Science | Scoop.it

The p53 gene is the major tumor suppressor in humans and is generally found mutated in over 50% of all human cancers.

 

The dominant-negative (DN) effect of the mutant p53 gene in cancers was found to affect the outcome of cancer treatment modalities. DN effect is a phenomenon whereby one copy of mutant p53 that exists in cancer cells inhibits the tumor suppressor activity of the other wild-type p53 copy when they co-exist. The result is that a patient may either have poor response or earlier relapse of tumours after their treatment.

 

The research findings is significant in that it offers hope to improve cancer treatment outcomes by selectively inhibiting mutant p53's DN effect through several methods by generating selective and specific inhibitory molecules specific for some of the common hot-spot p53 point mutations. There are currently no drugs or compounds that can alleviate DN effects of mutant p53.

 

In order to understand the specific roles of mutant p53 DN properties in regulating acute treatment response and long-term tumourgenesis, a team of five researchers led by NCCS Prof Kanaga Sabapathy, the Principal Investigator in the Laboratory of Carcinogenesis and Head of the Division of Cellular & Molecular Research from NCCS, carried out experiments by generating genetically engineered knock-in mouse strains expressing varying levels of mutant p53. The results showed that DN effect is observed after acute p53 activation by a variety of chemotherapeutic drugs and irradiation, thereby affecting anti-cancer treatment.

 

It was found that mutant p53 have DN effects in a cell-type and dose-dependent manner, especially during acute p53 activation where p53 levels are elevated. Based on the above observations, efforts to generate specific inhibitors for the common hot spot p53 point mutations are underway. The inhibition of mutant p53 expression in cells carrying a wild-type and mutant p53 alleles can improve response to chemotherapeutic drugs.

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Long non-coding RNA molecule "Braveheart" necessary to regulate differentiation of embryonic stem cells into cardiac cells

Long non-coding RNA molecule "Braveheart" necessary to regulate differentiation of embryonic stem cells into cardiac cells | Amazing Science | Scoop.it
When the human genome was sequenced, biologists were surprised to find that very little of the genome—less than 3 percent—corresponds to protein-coding genes. What, they wondered, was all the rest of that DNA doing?

 

It turns out that much of it codes for genetic snippets known as long non-coding RNAs, or lncRNAs. In recent years, scientists have found that these molecules often help to regulate which genes get turned on or off inside a cell. However, little is known about the specific roles of the thousands of lncRNAs discovered so far. In a new study, MIT biologists have identified a critical role for a lncRNA they dubbed "Braveheart." This lncRNA appears to stimulate stem cells to transform into heart cells during mouse embryonic stem cell (ESC) differentiation; the researchers suspect that lncRNAs may control this process in humans as well. If so, learning more about lncRNAs could offer a new approach to developing regenerative drugs for patients whose hearts have been damaged by cardiovascular disease or aging. "It opens a new door to what we could do, and how we could use lncRNAs to induce specific cell types, that's been completely unexplored," says Carla Klattenhoff, a postdoc in MIT's Department of Biology and one of the lead authors of a paper describing the findings in the Jan. 24 online edition of Cell. MIT postdoc Johanna Scheuermann is also a lead author of the paper. Senior author is Laurie Boyer, the Irwin and Helen Sizer Career Development Associate Professor of Biology at MIT. The researchers zeroed in on the Braveheart lncRNA because they had noticed that it is abundant both in ESCs and in differentiating heart cells. In the new study, they found that without normal levels of the Braveheart lncRNA, mouse ESCs did not develop any of the three major types of heart cells that comprise the cardiovascular system—cardiomyocytes (which make up cardiac muscle), smooth muscle cells and endothelial cells.

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Rare disease in Amish children sheds light on common neurological disorders

Rare disease in Amish children sheds light on common neurological disorders | Amazing Science | Scoop.it
So often the rare informs the common. Penn researchers investigating a regulatory protein involved in a rare genetic disease have shown that it may be related to epileptic and autistic symptoms in other more common neurological disorders.

 

A team of researchers from the University of Pennsylvania School of Medicine, led by Peter B. Crino, MD, PhD, associate professor of Neurology and director of the Penn Epilepsy Center, demonstrate how mutations in the STRAD-alpha gene can cause a disease called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy) syndrome, found in a handful of Amish children. PMSE is characterized by an abnormally large brain, cognitive disability, and severe, treatment-resistant epilepsy. Specifically, in an animal model, they found that the lack of the STRAD-alpha protein due to genetic mutations causes activation of the signaling pathway involving another protein called mTOR. In humans, this in turn may promote abnormal cell growth and cognitive problems in the developing brains of children. STRAD-alpha and mTOR proteins are part of a complex molecular network implicated in other, more common neurological disorders, many of which have autism-like symptoms as a component. "The identification of a new gene that regulates mTOR provides fascinating insights into how mTOR pathway dysfunction may be associated with neurological disorders," says Crino. "Each new mTOR regulatory protein that is identified provides a new possible therapeutic target for drug development and treatment."

 

The mTOR pathway normally controls cell growth, but in PMSE uncontrolled mTOR signaling leads to increases in brain size and areas in which the cerebral cortex is malformed. To prove this, the researchers knocked down the activity of the STRAD-alpha protein in a mouse model and caused malformations of the developing brain. The structure of these malformations was similar to what is seen in human PMSE and TSC and supports the conclusion that normal brain development in part depends on normal STRAD-alpha function. Localized brain malformations are among the most common causes of epilepsy and neurological disability in children.

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Thousands Of Years Old Chinese Medicinal Herb Chang Shan Works Through Aminoacylation

Thousands Of Years Old Chinese Medicinal Herb Chang Shan Works Through Aminoacylation | Amazing Science | Scoop.it

The mysterious inner workings of Chang Shan—a Chinese herbal medicine used for thousands of years to treat fevers associated with malaria—have been uncovered thanks to a high-resolution structure solved at The Scripps Research Institute (TSRI). Chang Shan, also known as Dichroa febrifuga Lour, probably helps with malarial fevers because traces of a halofuginone-like chemical in the herb interfere with this same process in malaria parasites, killing them in an infected person’s bloodstream. 

 

The structure shows in atomic detail how a two-headed compound derived from the active ingredient in Chang Shan works. Scientists have known that this compound, called halofuginone (a derivative of the febrifugine), can suppress parts of the immune system—but nobody knew exactly how. 

 

The new structure shows that, like a wrench in the works, halofuginone jams the gears of a molecular machine that carries out “aminoacylation,” a crucial biological process that allows organisms to synthesize the proteins they need to live.

 

Aminoacylation is the biological process whereby the amino acid’s pearls are attached to these tRNA shuttles. A class of enzymes known as aminoacyl-tRNA synthetases is responsible for attaching the amino acids to the tRNAs, and Schimmel and his colleagues have been examining the molecular details of this process for years. Their work has given scientists insight into everything from early evolution to possible targets for future drug development. 

 

Over time what has emerged as the picture of this process basically involves three molecular players: a tRNA, an amino acid and the aminoacyl-tRNA synthetase enzyme that brings them together. A fourth molecule called ATP is a microscopic form of fuel that gets consumed in the process.

 

The new work shows that halofuginone gets its potency by interfering with the tRNA synthetase enzyme that attaches the amino acid proline to the appropriate tRNA. It does this by blocking the active site of the enzyme where both the tRNA and the amino acid come together, with each half of the halofuginone blocking one side or the other.

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Regulators approve new Baculovirus-encoded insect cell-produced flu vaccine

Regulators approve new Baculovirus-encoded insect cell-produced flu vaccine | Amazing Science | Scoop.it

As flu season rages across the United States, federal regulators say they have approved a new kind of vaccine for the virus.

 

The new product, Flublok, which is available in limited supplies for the current season, is different from other flu vaccines, because it isn't made using eggs or an influenza virus, the Food and Drug Administration said Wednesday.

 

Instead, Flublok's production involves programming insect cells grown in steel tanks to produce large amounts of a particular flu virus protein, known as hemagglutinin, according to Protein Sciences, the vaccine's manufacturer.

Most human antibodies that fight flu infection are directed against hemagglutinin, the FDA said.

 

Flu vaccine attitudes abroad differ from U.S. This method allows for more rapid production, making more of the vaccine available more quickly in the event of a pandemic, the FDA said.

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