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Scooped by Dr. Stefan Gruenwald!

Robust ‘spider silk’ matrix guides cardiac tissue regeneration

Robust ‘spider silk’ matrix guides cardiac tissue regeneration | Amazing Science |

Genetically engineered fibers of the protein spidroin — the construction material for spider webs — are a ideal matrix (substrate or frame) for cultivating heart tissue cells, Moscow Institute of Physics and Technology (MIPT) researchers have found, as noted in an open-access article in the journal PLOS ONE.

Regenerative methods can solve the problem of transplant rejection, but it’s a challenge to find a suitable matrix to grow cells on: The material should be non-toxic, elastic, and not rejected by the body or impede cell growth. KurzweilAI has reported on a number of solutions.

Researchers led by Professor Konstantin Agladze, who heads the Laboratory of the Biophysics of Excitable Systems at MIPT, have been cultivating tissues that contract and conduct excitation waves, from cells called cardiomyocytes.

They decided to explore using synthetic electrospun fibers of spidroin as a matrix. They’re light, five times stronger than steel, twice more elastic than nylon, and are capable of stretching a third of their length. Which is why they are currently used as a substrate to grow implants like bones, tendons and cartilages, as well as dressings.

But could they are also function for soft tissues, such as the heart? Agladze decided to find out. His team seeded isolated neonatal rat cardiomyocytes on fiber matrices.  Using a microscope and fluorescent markers, the researchers monitored the growth of the cells and tested their contractibility and the ability to conduct electric impulses, which are the main features of normal cardiac tissue. Within three to five days a layer of cells formed on the substrate. They were able to contract synchronously and conduct electrical impulses just like the tissue of a living heart would.

“Cardiac tissue cells successfully adhere to the substrate of recombinant spidroin,” Agladze says. “They grow forming layers and are fully functional, which means they can contract coordinately.”

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New Sickle Cell Gene Therapy Approaches

New Sickle Cell Gene Therapy Approaches | Amazing Science |

As a patient prepares to become the first in history to receive his own genetically engineered stem cells for sickle cell disease, two top scientists are already improving the approach. The team of University of California, Los Angeles (UCLA) immunologist Donald Kohn will soon be adding a healthy version of the hemoglobin, beta (HBB) gene, mutated in sickle cell, to blood stem cells his team will have taken from a patient’s bone marrow, according to Kohn. Then his team will give the corrected stem cells back. Kohn’s team is confident, given that the same approach—adding a gene to cells with one gene mutation—has been succeeding in two of Kohn’s (also pioneering) adenosine deaminase-severe combined immunodeficiency (ADA-SCID) gene therapy trials.

Meanwhile, both he and hematologist Linzhau Cheng of Johns Hopkins University published papers this month that went further, correcting the mutation in sickle cell blood cells. “Both studies for developing next-generation gene correction of sickle cell disease are worthy,” Cheng told Drug Discovery & Development. “These are significant steps forward from the previous gene therapy strategies: using viral vectors to add a copy of genes into hematopoietic stem and progenitor cells.”

Kohn’s team reported on two clinical trials, in which they gave a healthy ADA gene to patients with ADA-SCID, at the end of February at the American Society for Blood and Marrow Transplantation meeting. In a Phase 2 study, patients aged three months to 15 years were given their own blood stem cells back after a healthy version of the ADA gene was introduced to their cells via a retroviral vector. As a result of that 2009 to 2014 trial, nine of ten patients are still off enzyme replacement therapy, and three were able to discontinue intravenous immunoglobulin (IVIg). In May 2013, Kohn started a new ADA gene therapy trial, this time using a next-gen technology, a self-inactivating lentiviral vector considered safer. Eight patients, aged four to 42 months old, have been enrolled. The six who are more than 30 days out are all off enzyme replacement therapy.

In Blood this month, Kohn reported he has been working on a more precise approach: correcting the mutation using zinc finger nucleases (ZFNs). His approach is different from that of Cheng, who reports in Stem Cells he corrected the mutation, too, if by reprogramming adult blood cells into proliferating induced pluripotent stem cells (iPSCs), then using the popular CRISPR/cas9 technique.

Kohn told Drug Discovery & Development his team used ZFNs as “we started this work about four to five years ago when they were the main method” of gene editing. The third of the Big Three gene editing technologies, TALENs, was “just coming into use, and CRISPR was not even developed.”

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Antibody shows promise as treatment for HIV

Antibody shows promise as treatment for HIV | Amazing Science |

Treating HIV with an antibody can reduce the levels of the virus in people's bodies — at least temporarily, scientists report on 8 April in Nature1The approach, called passive immunization, involves infusing antibodies into a person's blood. Several trials are under way in humans, and researchers hope that the approach could help to prevent, treat or even cure HIV. The work is a milestone towards those goals, says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. “This is an early study, but it’s a study with some impressive results,” he says.

Researchers tested four different doses of an HIV antibody called 3BNC117 in 29 people in the United States and Germany. Seventeen of the participants had HIV, and 15 of those were not taking antiretroviral (ARV) drugs at the time of the study. One infusion of the highest dose of antibody, given to 8 participants, cut the amount of virus in their blood by between 8 and 250 times for 28 days.

But much work remains to determine whether the approach can produce longer-lasting effects and whether it is practical for clinical use. Previous studies have shown that passive immunization can reduce levels of HIV in the blood of monkeys and mice, although the approach has not worked as well in humans2.

But the antibodies used in those earlier clinical tests were of an older generation that could not neutralize many different strains of HIV. Researchers have spent much of the past decade trying to find 'broadly neutralizing' antibodies that are more widely effective against the virus, and the 3BNC117 antibody belongs to this class.

The price of treatment with this approach is also a concern. Antibodies can cost thousands of dollars for each course of treatment, and the majority of people with HIV are in low- and middle-income countries, some of which are already fighting drug companies over the high cost of antibody medicines. “The practicality, utility and efficacy of this approach are hugely open questions,” says Mitchell Warren, executive director of AVAC, a global organization that advocates HIV prevention and is headquartered in New York City.

Brian sedano's comment, March 2, 9:56 PM
This article talks about how antibody can cure Hiv. Also it can cure virus in the body. passive immunization, involves infusing antibodies into a persons blood. This could help cure most of the virus in he body. But there is much work for it could be able to cure some of the viruses. But the problem is ut could cost thousands of dollars. most people that have hiv can hardly afford it and that could be a problem.Overall this article was interesting. Im hoping to read more about how the cure can be cheaper and easier to use!
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Personalized cancer vaccines pass early tests and may be used to fight tumors

Personalized cancer vaccines pass early tests and may be used to fight tumors | Amazing Science |

Cancer treatments that harness the body’s immune system to wipe out tumors have begun paying off for some patients for whom all other therapies have failed. Now, a small clinical study has found support for a newcomer on the cancer immunotherapy front. Injected with a vaccine designed to match specific mutations in their tumors, three patients with advanced melanoma had a strong immune response and in two their tumors shrunk or stabilized, at least temporarily. Although the study was mainly meant to test safety, the results suggest it holds promise for stopping tumors from growing.

“There’s a lot of excitement about this approach,” says oncologist and cancer immunologist Craig Slingluff of the University of Virginia in Charlottesville, who was not involved with the study. Vaccines for infectious diseases typically deliver into the body bits of protein or other material from a virus or bacterium that trigger the immune system to defend against the invading pathogen. With cancer, the similar idea is to vaccinate a patient with immune-stimulating molecules, known as antigens, found only on tumor cells, so that the person’s immune system ends up attacking the tumor. But cancer vaccines have a poor record of success. That’s because most of the tumor antigens tested also appear in small amounts on healthy cells, and the immune system has mechanisms that make it tolerate, or ignore, these familiar antigens.

Scientists have their eye on a more promising kind of tumor antigen: those that result from the mutations that riddle a tumor’s DNA, thanks to the chaos cancer causes to a genome. Some of these mutations do not appear in genes that drive cancer growth, but instead code for novel peptides—short proteins—that may act as antigens on the surface of tumor cells. Because these so-called neoantigens are completely foreign to the body, they could in theory make a cancer vaccine.

Devising a neoantigen cancer vaccine requires sequencing a lot of tumor DNA, which wasn’t feasible or affordable until recently. But now that DNA sequencing costs have dropped and speeds increased, researchers at Washington University in St. Louis have begun exploring neoantigen cancer vaccines for melanoma, a tumor in which the sun’s ultraviolet light that sparks cancer-causing mutations also creates hundreds of additional mutations that are likely to include many coding for neoantigens.

Human immunologist Beatriz Carreno, trial leader Gerald Linette, and collaborators recently studied three melanoma patients who had surgery to remove their tumors, but who had cancer cells that had spread to their lymph nodes, making tumors likely to recur. The researchers sequenced the exome, or protein-coding DNA, of each patient’s original melanoma tumor and compared it with the exome of their other cells to identify dozens of mutations coding for newly created peptides that might act as neoantigens. (Not all peptides made by a cell get displayed on its surface.) They analyzed the possible neoantigens’ structures and did lab tests to predict which are actually made by the cell and get displayed on its surface, then homed in on those most likely to trigger an immune response. For each melanoma patient they chose seven neoantigens unique to that person’s tumor.

After taking blood from each patient and harvesting from it immune sentinels called dendritic cells, the researchers then mixed each patient’s set of neoantigens with these white blood cells so that they would display the peptides to other immune cells. The team used the neoantigen-coated dendritic cells to make personalized neoantigen vaccines that were infused into the patients three times over about 4 months.

Carreno and collaborators found that a key measure of vaccine response, the number of immune system T cells specific to the neoantigens in each patient, rose in the patients’ blood, along with an increase in the diversity of these T cells. These neoantigen-specific T cells could also kill cultured melanoma cells expressing the same neoantigens, the team reports in Science.

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Fish Oil Claims are Not Supported by Research Studies

Fish Oil Claims are Not Supported by Research Studies | Amazing Science |

Fish oil is now the third most widely used dietary supplement in the United States, after vitamins and minerals, according to a recent report from the National Institutes of Health. At least 10 percent of Americans take fish oil regularly, most believing that the omega-3 fatty acids in the supplements will protect their cardiovascular health. But there is one big problem: The vast majority of clinical trials involving fish oil have found no evidence that it lowers the risk of heart attack and stroke.

From 2005 to 2012, at least two dozen rigorous studies of fish oil were published in leading medical journals, most of which looked at whether fish oil could prevent cardiovascular events in high-risk populations. These were people who had a history of heart disease or strong risk factors for it, like high cholesterol, hypertension or Type 2 diabetes.

All but two of these studies found that compared with a placebo, fish oil showed no benefit. And yet during this time, sales of fish oil more than doubled, not just in the United States but worldwide, said Andrew Grey, an associate professor of medicine at the University of Auckland in New Zealand and the author of a 2014 study on fish oil in JAMA Internal Medicine.

“There’s a major disconnect,” Dr. Grey said. “The sales are going up despite the progressive accumulation of trials that show no effect.”

In theory at least, there are good reasons that fish oil should improve cardiovascular health. Most fish oil supplements are rich in two omega-3 fatty acids — eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) — that can have a blood-thinning effect, much like aspirin, that may reduce the likelihood of clots. Omega-3s can also reduce inflammation, which plays a role in atherosclerosis. And the Food and Drug Administration has approved at least three prescription types of fish oil — Vascepa, Lovaza and a generic form — for the treatment of very high triglycerides, a risk factor for heart disease.

But these properties of omega-3 fatty acids have not translated into notable benefits in most large clinical trials.

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'Google Maps' for the body: A biomedical revolution down to a single cell

'Google Maps' for the body: A biomedical revolution down to a single cell | Amazing Science |
Scientists are using previously top-secret technology to zoom through the human body down to the level of a single cell. Scientists are also using cutting-edge microtome and MRI technology to examine how movement and weight bearing affects the movement of molecules within joints, exploring the relationship between blood, bone, lymphatics and muscle.

UNSW biomedical engineer Melissa Knothe Tate is using previously top-secret semiconductor technology to zoom through organs of the human body, down to the level of a single cell.

A world-first UNSW collaboration that uses previously top-secret technology to zoom through the human body down to the level of a single cell could be a game-changer for medicine, an international research conference in the United States has been told.

The imaging technology, developed by high-tech German optical and industrial measurement manufacturer Zeiss, was originally developed to scan silicon wafers for defects.

UNSW Professor Melissa Knothe Tate, the Paul Trainor Chair of Biomedical Engineering, is leading the project, which is using semiconductor technology to explore osteoporosis and osteoarthritis.

Using Google algorithms, Professor Knothe Tate -- an engineer and expert in cell biology and regenerative medicine -- is able to zoom in and out from the scale of the whole joint down to the cellular level "just as you would with Google Maps," reducing to "a matter of weeks analyses that once took 25 years to complete."

Her team is also using cutting-edge microtome and MRI technology to examine how movement and weight bearing affects the movement of molecules within joints, exploring the relationship between blood, bone, lymphatics and muscle. "For the first time we have the ability to go from the whole body down to how the cells are getting their nutrition and how this is all connected," said Professor Knothe Tate. "This could open the door to as yet unknown new therapies and preventions."

Professor Knothe Tate is the first to use the system in humans. She has forged a pioneering partnership with the US-based Cleveland Clinic, Brown and Stanford Universities, as well as Zeiss and Google to help crunch terabytes of data gathered from human hip studies. Similar research is underway at Harvard University and Heidelberg in Germany to map neural pathways and connections in the brains of mice.

The above story is based on materials provided by University of New South Wales.

CineversityTV's curator insight, March 30, 2015 8:53 PM

What happens with the metadata? In the public domain? Or in the greed hands of the elite.

Courtney Jones's curator insight, April 2, 2015 4:49 AM

,New advances in biomedical technology

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Something Smells Fishy? New Device Sniffs Out Seafood Fraud

Something Smells Fishy? New Device Sniffs Out Seafood Fraud | Amazing Science |

Handheld instrument does real-time nucleic acid testing to check if you're getting the fish you paid for.

Appreciate a well-cooked tuna steak or salmon wrapped in a sushi roll? There’s a good chance the fish sitting on your plate or in your grocery store’s seafood case is not what its label says it is, according to the ocean conservancy group Oceana. So you could be paying a premium for red snapper that’s really just plain old tilapia.

University of South Florida scientists have now made a handheld device that could help fight such seafood fraud. The instrument genetically verifies whether fish being called grouper is really grouper or less expensive, potentially harmful substitutes like catfish or mackerel. A quarter of grouper in the United States is mislabeled, according to Oceana, making it the fourth most commonly mislabeled fish in the country. Snapper was the most commonly mislabeled.

The Oceana study found that 33 percent of the 1200-plus seafood samples taken nationwide were mislabeled. This seafood fraud costs fishermen, the U.S. seafood industry, and consumers $20–25 billion annually, it calculates. In addition, fraud allows illegally caught fish to slip into the legal seafood trade and prevents consumers from making ecologically-friendly choices.

Today’s DNA barcoding methods for seafood identification analyze a sample’s DNA. While the price of gene sequencing has dropped in recent years, it still takes days and expensive lab equipment for accurate genetic identitification. The new device, on the other hand, purifies and amplifies a seafood sample’s RNA, or ribonucleic acid. The assay is simpler and works within 90 minutes. USF marine science professor John Paul and his colleagues have developed such assays to identify several microorganisms, and have now applied the technology to seafood identification. 

The researchers described the technology and its application in the journal Food Control. They are now developing assays for other commercially relevant species, and they’re also commercializing it through Tampa-based spinoff PureMolecular LLC. That company plans to start selling the machines for US $2000 by this summer, Reuters reports.

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Could a 3D printer just make your next organ?

Could a 3D printer just make your next organ? | Amazing Science |

With 3D printers everywhere, making everything from Yoda statues to bionic body parts, this company is using 3D printing to make new body tissue. BioBots, a team from the University of Pennsylvania, does just that. They’ve developed a $5,000 3D printer that actually prints functional living tissue. The company just snagged the Most Innovative Company at SXSW’s Accelerator Awards.

And while most of the living tissue BioBots is creating these days is for drug research — to make it less expensive and take animals out of the mix — one day, it could print new organs for transplants. “If we could somehow reveal the failures before testing drugs on people, we would be able to identify false positives much earlier in the drug development process,” CEO and co-founder Danny Cabrera told Forbes. “The problem is in animal testing – mice are not humans, and tests on animals often fail to mimic human diseases or predict how the human body responds to new drugs.

“The Holy Grail is to develop fully functioning replacement organs out of a patient’s own cells, eliminating the organ waiting list, but in the meantime we’ll settle for getting more drugs approved by the FDA at a significantly lower cost on an accelerated time scale, improving the quality of life for millions of people around the world.”

Gary Yuen's curator insight, March 26, 2015 6:18 PM

For now, printing fully-functional organs to be transplanted is still in development, only using mice as test subjects. But it's a start, in the future, a machine may be able to produce the organ you need without you having to wait in line for an organ donor.

Patrick Bolter's curator insight, March 27, 2015 3:31 AM

With 3D printers becoming more and more advanced, it is becoming feasible to create specialised ones that will be capable of printing things like body tissue. I believe this will become a big area in technology in the coming decade.

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For heart repair, use microRNA

For heart repair, use microRNA | Amazing Science |

When people suffer a heart attack, they can’t regrow muscle cells that have died after being deprived of oxygen. But mice injected with small RNA molecules following heart attacks do regenerate cardiac muscle, researchers report in the March 18 Science Translational Medicine.

Scientists knew that a cluster of microRNAs, tiny molecules that keep genes from being turned on, are active in animal embryos at the same time that heart cells grow and divide. The RNA suppresses signals that tell organs to stop making new cells, a team of American and Chinese researchers found.

When the researchers deleted the microRNA group in mouse embryos, the rodents had less cell growth during the early stages of development. Making the microRNAs more active led to mice born with overlarge hearts.

The researchers then switched on production of the RNA molecules in adult mice that had suffered heart attacks. The rodents grew back heart muscle cells and had little scarring, which normally prevents the healing heart from contracting well.

After six to 12 weeks, though, the rodents’ hearts failed. “The muscle cells would continue to want to divide, and dividing cells don’t contract as well as nondividing cells,” says study coauthor Edward Morrisey, a developmental biologist at the University of Pennsylvania.

But when Morrisey and his team injected post–heart attack mice for seven days with short-lived molecules that simulate the effects of the microRNA, most of the animals survived.

“This is probably going to be a very useful way to promote cardiac regeneration, but the timing of it’s going to be really critical,” Morrisey says. “You’re going to want to do it for a very short window of time after cardiac injury.”

Next, Morrisey wants to see if the technique works in larger animals such as pigs.

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A new antibiotic kills pathogens without detectable resistance

A new antibiotic kills pathogens without detectable resistance | Amazing Science |

Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s.

Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. A group of scientists has now developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. They report in Nature a new antibiotic called teixobactin, which was discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). The scientists did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

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Future of bio-sensors: Ballpoint pens loaded with sensor-laden inks could eliminate finger pricks for diabetics

Future of bio-sensors: Ballpoint pens loaded with sensor-laden inks could eliminate finger pricks for diabetics | Amazing Science |

It means a small sketch on your skin could test your blood-sugar levels. Ballpoint pens loaded with sensor-laden inks could eliminate finger pricks for diabetics, and help them test their blood glucose levels simply by drawing cartoons - or just a few dots - on their skin. The innovative new ink could also be used to test for pollutants in the environment by drawing on leaves or on buildings' surfaces, and could help soldiers search for explosives and chemical weapons, the developers say. 

The team of engineers from the University of California, San Diego, who developed the ink, used it to fill up regular, off-the-shelf ballpoint pens. The aim was to enable a new type of do-it-yourself sensor with rapid diagnostic capabilities for people with diabetes. 

The ink is made from the enzymes glucose oxidase, which responds to sugar in the blood, and tyrosinase, which can help detect common pollutants known as phenols. These compounds are found in cosmetics and can be toxic at high enough concentrations.   

Charles Choi explains for IEEE Spectrum what else was needed to make the inks operate like on-demand sensors: “To make these bio-inks serve as electrodes, they added electrically conductive graphite powder. They also added: chitosan, a clotting agent used in bandages, to help the ink stick to surfaces; xylitol, a sugar substitute, to help stabilize the enzymes during chemical reactions; and biocompatible polyethylene glycol, which is used in several drug delivery applications, to help bind all these ingredients together.” 

The team has described its "enzymatic ink" and do-it-yourself sensor in the journalAdvanced Healthcare Materials.  Using their pens, they were able to draw sensors to measure glucose directly onto the wrist of a willing participant. They say this ink drawing could be “easily interfaced with a Bluetooth-enabled” device that can provide the read-out.

The researchers also used the ink to draw on and measure chemicals on leaves, and according to Choi at IEEE Spectrum, “the inks could be modified to react with many other pollutants, such as heavy metals or pesticides”. 

The main purpose of the ink, and probably the most immediate impact, will be to enable multiple-use testing strips for diabetes monitoring. As the authors note in their paper, handheld glucose meters rely on single use sensor strips, and each test is expensive for the user. 

Peter Hughes's curator insight, March 27, 2015 1:47 AM

This technology will undoubtedly be one of the greatest creations of the 21st century. The ability to test ones blood by drawing on their skin with a pen almost seems impossible, and yet scientists are making it a reality. Who knows what this could develop into; it could be used for identification, easy credit payments and so much more.

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Researchers unlock the mysteries of how cells rush to a wound and heal it

Researchers unlock the mysteries of how cells rush to a wound and heal it | Amazing Science |

A multidisciplinary research team has discovered how cells know to rush to a wound and heal it -- opening the door to new treatments for diabetes, heart disease and cancer. The findings shed light on the mechanisms of cell migration, particularly in the wound-healing process. The results represent a major advancement for regenerative medicine, in which biomedical engineers and other researchers manipulate cells' form and function to create new tissues, and even organs, to repair, restore or replace those damaged by injury or disease.

The answer, it turns out, involves delicate interactions between biomechanical stress, or force, which living cells exert on one another, and biochemical signaling. The University of Arizona researchers discovered that when mechanical force disappears -- for example at a wound site where cells have been destroyed, leaving empty, cell-free space -- a protein molecule, known as DII4, coordinates nearby cells to migrate to a wound site and collectively cover it with new tissue. What's more, they found, this process causes identical cells to specialize into leader and follower cells. Researchers had previously assumed leader cells formed randomly. "The results significantly increase our understanding of how tissue regeneration is regulated and advance our ability to guide these processes," said Pak Kin Wong, UA associate professor of mechanical and aerospace engineering and lead investigator of the research.

Wong's team observed that when cells collectively migrate toward a wound, leader cells expressing a form of messenger RNA, or mRNA, genetic code specific to the DII4 protein emerge at the front of the pack, or migrating tip. The leader cells, in turn, send signals to follower cells, which do not express the genetic messenger. This elaborate autoregulatory system remains activated until new tissue has covered a wound.

The same migration processes for wound healing and tissue development also apply to cancer spreading, the researchers noted. The combination of mechanical force and genetic signaling stimulates cancer cells to collectively migrate and invade healthy tissue.

Biologists have known of the existence of leader cells and the DII4 protein for some years and have suspected they might be important in collective cell migration. But precisely how leader cells formed, what controlled their behavior, and their genetic makeup were all mysteries -- until now. "Knowing the genetic makeup of leader cells and understanding their formation and behavior gives us the ability to alter cell migration," Wong said.

With this new knowledge, researchers can re-create, at the cellular and molecular levels, the chain of events that brings about the formation of human tissue. Bioengineers now have the information they need to direct normal cells to heal damaged tissue, or prevent cancer cells from invading healthy tissue.

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Current bird flu in China could become ‘pandemic’ threat to humans, researchers say

Current bird flu in China could become ‘pandemic’ threat to humans, researchers say | Amazing Science |

The virus causing a second wave of bird flu across China has mutated frequently and "should be considered as a major candidate to emerge as a pandemic strain in humans," researchers reported Wednesday.

While it is much too early to predict whether that might happen, one of the scientists said in an interview, there is cause for alarm because the H7N9 virus jumps to humans more quickly than its predecessors and previously has been found in mammals.

"This virus is more dangerous," said Yi Guan of the University of Hong Kong, one of the authors of a research letter published online Wednesday in the journal Nature.

It's not clear why the outbreak, which began in late 2013, has re-emerged after fading. But by September 2014, it had infected 318 people and killed more than 100 of them, twice as many as the first wave, the scientists reported. Many people suffer severe pneumonia if infected by this flu, which also has spread to China, Taiwan, Hong Kong, Malaysia and Canada, according to the World Health Organization.

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Woman's 'Burning Mouth Syndrome' Caused by HSV-1

Woman's 'Burning Mouth Syndrome' Caused by HSV-1 | Amazing Science |

An otherwise healthy 65-year-old woman developed a relentless burning sensation in her mouth that stumped doctors and dentists for months before its strange cause was found, according to a recent report of her case. The burning got worse whenever the woman brushed her teeth but subsided within 10 minutes. The pain went away after one month after she first experienced it, but then returned a year later and remained constant. She saw a dentist, an oral surgeon and her family doctor, but none of them could find any lesions in the mouth or other possible causes of the burning.

They prescribed mouthwashes, milk-of-magnesia rinses and anti-anxiety drugs, and recommended avoiding toothpaste with whitening agents. But nothing relieved the burning sensation. The woman had a case of a condition called "burning mouth syndrome," which is a chronic, burning sensation inside the mouth, usually in the lips, tongue or palate, according to the study, published April 1 in the journal BMJ Case Reports.

"It's common in postmenopausal women, and affects up to 7 percent of the general population," said study co-author Dr. Maria Nagel, a neuro-virologist and professor at the University of Colorado School of Medicine in Aurora. Nagel compared the feeling to a "sunburn inside the mouth," adding that it feels similar to the pain caused by a tooth infection or a root canal.

The condition can be a side effect of certain drugs, but other cases have no apparent medical or dental cause, Nagel said. After the woman had experienced this pain for six months, doctors tested her saliva for the virus that causes oral herpes, the herpes simplex virus type 1 (HSV-1). The virus commonly causes cold sores around the mouth and lips, but the woman didn't have any cold sores.

The tests showed that the woman's saliva was swarming with the infectious particles. "If she'd had cold sores, it would have been obvious," Nagel told Live Science. "Most people don't think of HSV-1 as the potential cause of burning mouth syndrome, so they don't test for it. But it's easily treatable with antiviral medication," she said.

The woman began taking an antiviral drug, and her pain disappeared within five days. Follow-up tests of her saliva — done four weeks later, and again six months later — found no hint of the virus. A year and a half after finishing her treatment, the patient remains pain-free, researchers said.

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Novel BLAST Method Delivers Large Particles Into Cells at High Speed

Novel BLAST Method Delivers Large Particles Into Cells at High Speed | Amazing Science |

A newly developed device can deliver nanoparticles, enzymes, antibodies, bacteria and other “large-sized” cargo into mammalian cells at speeds up to 100,000 cells per minute.

A new device developed by UCLA engineers and doctors eventually help scientists study the development of disease, enable them to capture improved images of the inside of cells and lead to other improvements in medical and biological research.

The researchers created a highly efficient automated tool that delivers nanoparticles, enzymes, antibodies, bacteria and other “large-sized” cargo into mammalian cells at the rate of 100,000 cells per minute — significantly faster than current technology, which works at about one cell per minute.

The research, published online in Nature Methods on April 6, was led by Eric Pei-Yu Chiou, associate professor of mechanical and aerospace engineering and of bioengineering at the Henry Samueli School of Engineering and Applied Science. Collaborators included students, staff and faculty members from the engineering school and the David Geffen School of Medicine at UCLA.

Currently, the only way to deliver so-called large cargo, particles up to 1 micrometer in size, into cells is by using micropipettes, syringe-like tools common in laboratories, which is much slower than the new method. Other approaches for injecting materials into cells — such as using viruses as delivery vehicles or chemical methods — are only useful for small molecules, which are typically several nanometers in length.

The new device, called a biophotonic laser-assisted surgery tool, or BLAST, is a silicon chip with an array of micrometer-wide holes, each surrounded by an asymmetric, semicircular coating of titanium. Underneath the holes is a well of liquid that includes the particles to be delivered.

Researchers use a laser pulse to heat the titanium coating, which instantly boils the water layer adjacent to parts of the cell. That creates a bubble that explodes near the cell membrane, resulting in a large fissure — a reaction that takes only about one millionth of a second. The fissure allows the particle-filled liquid underneath the cells to be jammed into them before the membrane reseals. A laser can scan the entire silicon chip in about 10 seconds.

Chiou said the key to the technique’s success is the instantaneous and precise incision of the cell membrane. “The faster you cut, the fewer perturbations you have on the cell membrane,” said Chiou, who is also a member of the California NanoSystems Institute.

Inserting large cargo into cells could lead to scientific research that was previously not possible. For example, the ability to deliver mitochondria, could alter cells’ metabolism and help researchers study diseases caused by mutant mitochondrial DNA.

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High-resolution biosensor can report conditions from deep in the body

High-resolution biosensor can report conditions from deep in the body | Amazing Science |

A new microscopic shape-shifting probe capable of sensitive, high-resolution remote biological sensing has been developed by scientists at the National Institute of Standards and Technology (NIST) and the National Institutes of Health (NIH). If eventually put into widespread use, the design could have a major impact on research in medicine, chemistry, biology, and engineering and ultimately used in clinical diagnostics, according to the researchers. To date, most efforts to image highly localized biochemical conditions such as abnormal pH* and ion concentration — critical markers for many disorders — rely on various types of nanosensors that are probed using light at optical frequencies. But the light doesn’t reach far into the body, so the sensitivity and resolution of the resulting optical signals decrease rapidly with increasing depth into the body. That has limited most applications to more optically accessible regions.

Fluorescent and plasmonic labels and sensors have revolutionized molecular biology, helping visualize cellular and biomolecular processes. Increasingly, such probes are now being designed to respond to wavelengths in the near-infrared region, where reduced tissue autofluorescence and photon attenuation enable subsurface in vivo sensing. But even in the near-infrared region, optical resolution and sensitivity decrease rapidly with increasing depth. A team of scientists now presents a sensor design that obviates the need for optical addressability by operating in the nuclear magnetic resonance (NMR) radio-frequency spectrum, where signal attenuation and distortion by tissue and biological media are negligible, where background interferences vanish, and where sensors can be spatially located using standard magnetic resonance imaging (MRI) equipment.

The radio-frequency-addressable sensor assemblies presented here comprise pairs of magnetic disks spaced by swellable hydrogel material; they reversibly reconfigure in rapid response to chosen stimuli, to give geometry-dependent, dynamic NMR spectral signatures. The sensors can be made from biocompatible materials, are themselves detectable down to low concentrations, and offer potential responsive NMR spectral shifts that are close to a million times greater than those of traditional magnetic resonance spectroscopies. Inherent adaptability should allow such shape-changing systems to measure numerous different environmental and physiological indicators, thus providing broadly generalizable, MRI-compatible, radio-frequency analogues to optically based probes for use in basic chemical, biological, medical and engineering research.

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Radio-frequency-heated iron-oxide nanoparticles open the blood-brain barrier

Radio-frequency-heated iron-oxide nanoparticles open the blood-brain barrier | Amazing Science |

A new method of opening the blood-brain barrier (BBB) to deliver therapeutic molecules directly to the brain has been developed by researchers from the University of MontrealPolytechnique Montréal, and CHU Sainte-JustineThe BBB protects the brain from elements circulating in the blood that may be toxic to the brain, but currently, 98% of therapeutic molecules are unable to cross the BBB.

KurzweilAI has reported a number of recently developed techniques for delivering drugs to the blood-brain barrier, ranging from protein-based nanoparticles to most recently, ultrasound. But according to principal investigator Sylvain Martel, “previous techniques either open the BBB too wide, exposing the brain to great risks, or they are not precise enough, leading to scattering of the drugs and possible unwanted side effects.”

To open the BBB, the researchers used a cannulation technique to deliver iron-oxide magnetic nanoparticles to the surface of the middle cerebral artery of mice. In a previous study they showed that MRI could guide nanoparticles to a desired location. Then they applied a radio-frequency field, heating the nanoparticles, which then dissipated the heat, creating a mechanical stress on the BBB. That allowed for a temporary and localized opening of the barrier for diffusion of a visually identifiable dye (representing a drug) for approximately two hours into the brain.


CineversityTV's curator insight, April 6, 2015 5:39 PM

Opening Pandora's Box.

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‘Nanoneedles’ generate new blood vessels in mice, paving the way for new regenerative medicine

‘Nanoneedles’ generate new blood vessels in mice, paving the way for new regenerative medicine | Amazing Science |
Scientists have developed “nanoneedles” that have successfully prompted parts of the body to generate new blood vessels, in a trial in mice.

The researchers, from Imperial College London and Houston Methodist Research Institute in the USA, hope their nanoneedle technique could ultimately help damaged organs and nerves repair themselves and help transplanted organs  thrive.

In a trial described in Nature Materials, the team showed they could deliver nucleic acids DNA and siRNA to back muscles in mice. After seven days there was a six-fold increase in the formation of new blood vessels in the mouse back muscles, and blood vessels continued to form over a 14 day period.

The nanoneedles are tiny porous structures that act as a sponge to load significantly more nucleic acids than solid structures. This makes them more effective at delivering their payload. They can penetrate the cell, bypassing its outer membrane, to deliver nucleic acids without harming or killing the cell.

The nanoneedles are made from biodegradable silicon, meaning that they can be left in the body without leaving a toxic residue behind. The silicon degrades in about two days, leaving behind only a negligible amount of a harmless substance called orthosilicic acid.

The hope is that one day scientists will be able to help promote the generation of new blood vessels in people, using nanoneedles, to provide transplanted organs or future artificial organ implants with the necessary connections to the rest of the body, so that they can function properly with a minimal chance of being rejected.

“This is a quantum leap compared to existing technologies for the delivery of genetic material to cells and tissues,” said Ennio Tasciotti, Co-Chair, Department of Nanomedicine at Houston Methodist Research Institute and co-corresponding author of the paper.

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Fecal transplants successful for treating C. difficile infection

Fecal transplants successful for treating C. difficile infection | Amazing Science |

Distasteful as it sounds, the transplantation of fecal matter is more successful for treating Clostridium difficile infections than previously thought. The research, published in the open access journal Microbiome, reveals that healthy changes to a patient's microbiome are sustained for up to 21 weeks after transplant, and has implications for the regulation of the treatment.

Clostridium difficile infections are a growing problem, leading to recurrent cases of diarrhea and severe abdominal pain, with thousands of fatalities worldwide every year. The infection is thought to work by overrunning the intestinal microbiome - the ecosystem of microorganisms that maintain a healthy intestine.

Fecal microbiota transplantation was developed as a method of treating C. difficile infection, and is particularly successful in patients who suffer repeat infections. Fecal matter is collected from a donor, purified, mixed with a saline solution and placed in a patient, usually by colonoscopy.

Previous research has shown that the fecal microbiota of patients resembles that of the donor, but not much is known about the short and long term stability of fecal microbiota transplanted into recipients.

In this research, Michael Sadowsky and colleagues at the University of Minnesota collected fecal samples from four patients before and after their fecal transplants. Three patients received freshly prepared microbiota from fecal matter and one patient received fecal microbiota that had previously been frozen. All received fecal microbiota from the same pre-qualified donor.

The team compared the pre- and post-transplant fecal microbial communities from the four patients, as well as from 10 additional patients with recurring C. difficile infections, to the sequences of normal subjects described in the Human Microbiome Project. In addition, they looked at the changes in fecal bacterial composition in recipients over time, and compared this to the changes observed within samples from the donor.

Surprisingly, after transplantation, patient samples appeared to sustain changes in their microbiome for up to 21 weeks and remained within the spectrum of fecal microbiota characterized as healthy.

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New technique for sorting biomolecules could lead to more efficient diagnostics

New technique for sorting biomolecules could lead to more efficient diagnostics | Amazing Science |

Employing an ingenious microfluidic design that combines chemical and mechanical properties, a team of Harvard scientists has demonstrated a new way of detecting and extracting biomolecules from fluid mixtures. The approach requires fewer steps, uses less energy, and achieves better performance than several techniques currently in use and could lead to better technologies for medical diagnostics and chemical purification.

The biomolecule sorting technique was developed in the laboratory of Joanna Aizenberg, Amy Smith Berylson Professor of Materials Science at Harvard School of Engineering and Applied Sciences (SEAS) and Professor in the Department of Chemistry and Chemical BiologyAizenberg is also co-director of the Kavli Institute for Bionano Science and Technology and a core faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering, leading the Adaptive Materials Technologies platform there.

The new microfluidic device, described in a paper appearing today in the journal Nature Chemistryis composed of microscopic “fins” embedded in a hydrogel that is able to respond to different stimuli, such as temperature, pH, and light. Special DNA strands called aptamers, that under the right conditions bind to a specific target molecule, are attached to the fins, which move the cargo between two chemically distinct environments. Modulating the pH levels of the solutions in those environments triggers the aptamers to “catch” or “release” the target biomolecule.

After using computer simulations to test their novel approach, in collaboration with Prof. Anna C. Balazs from the University of Pittsburgh, Aizenberg’s team conducted proof-of-concept experiments in which they successfully separated thrombin, an enzyme in blood plasma that causes the clotting of blood, from several mixtures of proteins. Their research suggests that the technique could be applicable to other biomolecules, or used to determine chemical purity and other characteristics in inorganic and synthetic chemistry.

“Our adaptive hybrid sorting system presents an efficient chemo-mechanical transductor, capable of highly selective separation of a target species from a complex mixture—all without destructive chemical modifications and high-energy inputs,” Aizenberg said. “This new approach holds promise for the next-generation, energy-efficient separation and purification technologies and medical diagnostics.”

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New species of leprosy bacteria found

New species of leprosy bacteria found | Amazing Science |

Scientists have compared for the first time the genomes of the two bacteria species that cause leprosy. The study shows how the two species evolved from a common ancestor around 13.9 million years ago, and offers new insights into their biology that could lead to new treatments.

Leprosy is a chronic infection of the skin, peripheral nerves, eyes and mucosa of the upper respiratory tract, affecting over a quarter million people worldwide. Its symptoms can be gruesome and devastating, as the bacteria reduce sensitivity in the body, resulting in skin lesions, nerve damage and disabilities. Until recently, leprosy was attributed to a single bacterium, Mycobacterium leprae; we now suspect that its close relative, Mycobacterium lepromatosis, might cause a rare but severe form of leprosy. EPFL scientists have analyzed for the first time the complete genome of M. lepromatosis, and compared it to that of the major leprosy-causing bacterium.

Published in PNAS, the study reveals the origin and evolutionary history of both bacteria, and offers new insights into their biology, global distribution, and possibly treatment. Along with its mutilating symptoms, leprosy also carries a stigma, turning patients into social outcasts. Although we have been able to push back the disease with antibiotics, leprosy remains endemic in many developing countries today.

Leprosy can manifest itself in various forms, all thought to be caused by the bacterium M. leprae. But in 2008, a study showed considerable evidence that another species of bacterium, M. lepromatosis, causes a distinct and aggressive form of the disease called “diffuse lepromatous leprosy”, found in Mexico and the Caribbean.

The lab of Stewart Cole at EPFL’s Global Health Institute carried out a genome-wide investigation on M. lepromatosis. This complex and computer-heavy technique looks at the bacterium’s entire DNA, locating its genes along the sequence. Because M. lepromatosis cannot be grown in the lab and animal models for this version of leprosy do not exist yet, the scientists used an infected skin sample from a patient in Mexico to obtain the bacterium’s genetic material.

After extracting the DNA from the entire sample, the researchers had to separate the bacterial DNA from the patient’s. To do this, they used two genetic techniques: one that increased the bacterium’s DNA and another that decreased the human DNA. With the bacterium’s DNA isolated, the researchers were able to sequence it and read it. Once they had the complete sequence of the bacterium’s genome, they were able to compare it with the known genome of M. leprae, the bacterium responsible for the majority of leprosy cases.

The study found that the two species of bacteria are very closely related. The comparative genomics analysis could “backtrack” the history of their genes, and showed that the two bacteria have diverged 13.9 million years ago from a common ancestor with a similar genome structure, and possibly a similar lifestyle. That ancestor suffered a process known as “gene decay”, where over a long period of time and multiple generations, a large number of genes mutated, became non-functional, and eventually disappeared. The study showed that the two new species continued to lose genes but from different regions of their genomes, indicating that during their evolution they occupied different biological roles and mechanisms to ensure survival.

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Cambridge scientists grow ‘mini-lungs’ to aid the study of cystic fibrosis

Cambridge scientists grow ‘mini-lungs’ to aid the study of cystic fibrosis | Amazing Science |
Scientists at the University of Cambridge have successfully created ‘mini-lungs’ using stem cells derived from skin cells of patients with cystic fibrosis, and have shown that these can be used to test potential new drugs for this debilitating lung disease.

The research is one of a number of studies that have used stem cells – the body’s master cells – to grow ‘organoids’, 3D clusters of cells that mimic the behaviour and function of specific organs within the body. Other recent examples have been‘mini-brains’ to study Alzheimer’s disease and ‘mini-livers’ to model liver disease. Scientists use the technique to model how diseases occur and to screen for potential drugs; they are an alternative to the use of animals in research.

Cystic fibrosis is a monogenic condition – in other words, it is caused by a single genetic mutation in patients, though in some cases the mutation responsible may differ between patients. One of the main features of cystic fibrosis is the lungs become overwhelmed with thickened mucus causing difficulty breathing and increasing the incidence of respiratory infection. Although patients have a shorter than average lifespan, advances in treatment mean the outlook has improved significantly in recent years.

Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute used skin cells from patients with the most common form of cystic fibrosis caused by a mutation in the CFTR gene referred to as the delta-F508 mutation. Approximately three in four cystic fibrosis patients in the UK have this particular mutation. They then reprogrammed the skin cells to an induced pluripotent state, the state at which the cells can develop into any type of cell within the body.

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Imaging break-through: Fusion of microscopy and mass spectrometry produces detailed map of protein distribution

Imaging break-through: Fusion of microscopy and mass spectrometry produces detailed map of protein distribution | Amazing Science |

Vanderbilt University researchers have achieved the first “image fusion” of mass spectrometry and microscopy — a technical tour de force that could, among other things, dramatically improve the diagnosis and treatment of cancer. Microscopy can yield high-resolution images of tissues, but “it really doesn’t give you molecular information,” said Richard Caprioli, Ph.D., senior author of the paper published last week in the journal Nature Methods.

Mass spectrometry provides a very precise accounting of the proteins, lipids and other molecules in a given tissue, but in a spatially coarse or pixelated manner. Combining the best features of both imaging modalities allows scientists to see the molecular make-up of tissues in high resolution.

“That to me is just phenomenal,” said Caprioli, the Stanford Moore Professor of Biochemistry and director of the Mass Spectrometry Research Center. Caprioli said the technique could redefine the surgical “margin,” the line between cancer cells and normal cells where the scalpel goes to remove the tumor.

Currently that line is determined by histology — the appearance of cells examined under the microscope. But many cancers recur after surgery. That could be because what appear to be normal cells, when analyzed for their protein content using mass spectrometry, are actually cancer cells in the making. 

Using a mathematical approach called regression analysis, the researchers mapped each pixel of mass spectrometry data onto the corresponding spot on the microscopy image to produce a new, “predicted” image. It’s similar in concept to the line drawn between experimentally determined points in a standard curve, Caprioli said. There are no “real” points between those that were actually measured, yet the line is predicted by the previous experiments.

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Zapping Deadly Blood Clots Just Got a Thousand Times Faster

Zapping Deadly Blood Clots Just Got a Thousand Times Faster | Amazing Science |

Once the symptoms of a stroke begin—your face begins to droop, an arm feels suddenly weak, you find yourself struggling to speak—you have less than six hours to get to a medical center for treatment. That six hour window is the magic number: Patients treated soon after the onset of a stroke are more likely to survive and less likely to suffer disabilities after three months.

Fortunately, researchers at the Houston Methodist Research Institute have developed a new system that delivers brain-saving drugs up to 1,000 times faster using nanoparticles, miniscule magnetic objects that can ferry medication safely through our blood. he new research, published in the journal Advanced Functional Materials, introduces a method of tPA delivery that uses biodegradable nanoparticles (tPA-NC) to send the clot-busting tPA directly to the site of the dangerous clot. The particle is cloaked in the protein albumin; this camouflage allows it to move stealthily through the body, evading attack by the immune system.

At 150 nanometers wide each, the nanoparticles are almost mind-bogglingly small, roughly 1/50th the size of a human red blood cell.

For this experiment, researchers created an arterial clot in a mouse to study the effect of the particles in a live model. They found that, in addition to being much faster, the new method may reduce the overall risk of bleeding.

"We have designed the nanoparticles so that they trap themselves at the site of the clot, which means they can quickly deliver a burst of the commonly used clot-busting drug tPA where it is most needed," the study’s co-principal investigator, Paolo Decuzzi, explained to Science Daily.

This will allow doctors to use a lower dose of the drug, decreasing the risk of hemorrhage and opening up tPA treatment to patients previously considered ineligible for use of the drug due to their risk of bleeding. Because of the iron core, researchers believe these nanoparticles can be guided directly to the site of the clot using an external magnetic field, focusing the drug onto the dangerous clot and further reducing the risk of bleeding.

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New class of experimental cholesterol drugs might sharply reduce the risk of heart attacks and strokes

New class of experimental cholesterol drugs might sharply reduce the risk of heart attacks and strokes | Amazing Science |

A new class of experimental cholesterol drugs might sharply reduce the risk of heart attacks and strokes, researchers reported on Sunday, citing what they described as preliminary evidence.

The drugs, one being developed by Amgen and the other by Sanofi and Regeneron Pharmaceuticals, are already known to sharply reduce so-called bad cholesterol, sometimes to levels lower than those achieved by statins like Lipitor, the mainstay lipid-lowering medicines.

What has not been known before, however, is whether the drugs do what patients and doctors really care about: protect against heart attacks, strokes and other cardiovascular problems or “events.” The early results suggest that there might be such a benefit, maybe even a big one. In small studies sponsored by the manufacturers, both drugs reduced the rate of such cardiovascular problems by about half.

“To see a reduction in cardiovascular events already is very encouraging that we’re on the right track,” Dr. Jennifer G. Robinson, the lead investigator in the trial of the Sanofi drug, said in an interview.

The studies were published in The New England Journal of Medicine and were being presented at the annual meeting of the American College of Cardiology taking place through Monday in San Diego.

Researchers cautioned, however, that the studies were small and intended to assess whether the drugs lowered the bad cholesterol and were safe, not whether they staved off heart attacks. That could make the conclusions about heart attack and stroke risk less trustworthy. Judging those effects will require larger trials involving tens of thousands of people; such studies are underway and are expected to be completed by 2017.

“I do not think that either study answers the question definitively of cardiovascular benefit,” said Dr. Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, referring to the drug makers’ research. He was not involved in either study.

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