Experimental therapy restores normal fat metabolism in animals with atherosclerosis

 

In what may be a major leap forward in the quest for new treatments of the most common form of cardiovascular disease, scientists at Johns Hopkins report they have found a way to halt and reverse the progression of atherosclerosis in rodents by loading microscopic nanoparticles with a chemical that restores the animals' ability to properly handle cholesterol. Cholesterol is a fatty substance that clogs, stiffens and narrows the blood vessels, greatly diminishing their ability to deliver blood to the heart muscle and the brain. The condition, known as atherosclerotic vessel disease, is the leading cause of heart attacks and strokes that claim some 2.6 million lives a year worldwide, according to the World Health Organization. A report on the work, published online in the journal Biomaterials, builds on recent research by the same team that previously identified a fat-and-sugar molecule called GSL as the chief culprit behind a range of biological glitches that affect the body's ability to properly use, transport and purge itself of vessel-clogging cholesterol. That earlier study showed that animals feasting on high-fat foods remained free of heart disease if pretreated with a human-made compound, D-PDMP, which works by blocking the synthesis of the mischievous GSL. But the body's natural tendency to rapidly break down and clear out D-PDMP was a major hurdle in efforts to test its therapeutic potential in larger animals and humans. The newly published report reveals the scientists appear to have cleared that hurdle by encapsulating D-PDMP into tiny molecules, which are absorbed faster and linger in the body much longer. In this case, the researchers say, their experiments show that when encapsulated that way, D-PDMP's potency rose ten-fold in animals fed with it. Most strikingly, the team reports, the nano version of the compound was potent enough to halt the progression of atherosclerosis. By contrast, the team's previous research showed the drug was effective in preventing atherosclerosis but not potent enough to stop the disease from advancing. Perhaps, most importantly, the team says, the nano-packaged drug improved physiologic outcomes among animals with heart muscle thickening and pumping dysfunction, the hallmarks of advanced disease. "Our experiments illustrate clearly that while content is important, packaging can make or break a drug," says lead investigator Subroto Chatterjee, Ph.D., a professor of medicine and pediatrics at the Johns Hopkins University School of Medicine and a metabolism expert at its Heart and Vascular Institute. "In our study, the right packaging vastly improved the drug's performance and its ability not merely to prevent disease but to mitigate some of its worst manifestations." That added potency, the researchers say, stems from fast uptake by various tissues and organs and from the slow clearance of the encapsulated form of the drug. The team was able to map and track the nanoparticles' movement inside the animals' bodies by tagging them with a radioactive tracer that lit up on a CT scan. Next, to observe how quickly the body broke down the nano-wrapped and the original forms of the drug, researchers analyzed kidney samples from mice treated with either form of the compound. The kidneys are the final stop on most drugs' journey inside the body just before they are cleared through urine. The nano drug remained in animals much longer, around 48 hours, compared with the free form, which was excreted through the kidneys in about an hour. In further experiments, the scientists put mice genetically predisposed to atherosclerosis on a fat-laden diet for several months -- long enough for fatty plaque to accumulate inside their blood vessels. After a few months, a third of the animals began treatment with the nano-packaged compound, one-third with its native version, while the rest got placebo. Mice treated with placebo showed high levels of GSL -- the molecule responsible for altered cholesterol metabolism -- and high levels of bad cholesterol, or LDL. They also had dangerously high levels of oxidized LDL, an especially pernicious type of LDL formed when it encounters free radicals, and elevated triglycerides, another type of plaque-building fat. By contrast, animals given encapsulated D-PDMP had normal GSL and cholesterol levels as did animals treated with free-floating forms of the drug. However, animals treated with the free-floating form of D-PDMP required 10 times higher doses to achieve GSL and cholesterol levels observed in mice given the nano-encapsulated form of the drug. When scientists measured the thickness of the animals' aortas -- the body's largest vessel responsible for carrying oxygen-rich blood from the heart to the rest of the body -- they observed stark differences among the groups, they say. The aortas of placebo-treated animals had grown thicker with fat and calcium deposits. Mice treated with either version of the drug fared better, but animals that got the encapsulated form of the drug had aortas nearly indistinguishable from the aortas of healthy mice fed a regular diet, according to researchers. Most strikingly, they reported, D-PDMP treatment improved heart function in mice with advanced forms of atherosclerotic heart disease, marked by heart muscle thickening and compromised pumping ability. Ultrasound images revealed that both size and pumping ability improved in animals that received treatment with the encapsulated form of the drug, returning to near baseline levels. However, mice given non-encapsulated drug required 10 times higher doses to achieve similar benefits. High cholesterol occurs when the body gets too much of it from food, when it makes too much of it on its own, or due to a defect in the body's ability to ferry it in and out of cells or break it down. Current cholesterol-lowering treatments work either by blocking cholesterol production or by preventing the body from absorbing too much of it. But production and absorption are only two steps in the cholesterol cycle, Chatterjee says, so new treatments that interfere with other glitches in this cycle are badly needed. D-PDMP is one such treatment candidate because it blocks the synthesis of GSL -- the master regulator of multiple pathways involved in faulty fat metabolism, Chatterjee says. Researchers say their next step is to test how the drug performs in larger mammals. Because the nanoparticles carrying D-PDMP are made of a common laxative ingredient and a naturally occurring sebacic acid, researchers say they are completely safe for humans. D-PDMP, long used in basic research to experimentally block and study cell growth and other basic cell functions, is considered safe in animals, but its safety profile in humans is unknown, the investigators say.

Photo selection study reveals we don't look like we think we look

 

Credit: Courtesy of David White; CC BY SA. Be careful when choosing your next passport photo or profile image as a new study suggests we are so poor a picking good likenesses of our face that strangers make better selections. This is one of the findings of a study by Dr David White and colleagues from the UNSW Australia published today, Wednesday 24 June 2015, in the British Journal of Psychology. The study was supported by an Australian Research Council grants and funding from the Australian Passport Office. Dr White said: “In face-to-face encounters with unfamiliar people, it is often necessary to verify that we are who we claim to be. For example, we are asked to prove our identity when processing financial transactions and crossing borders. In these and many other commonplace situations, photo-ID is the most common method for identity verification. However, despite the clear importance of this visual task previous research has shown that we are quite poor when matching photos of unfamiliar faces.” In the study an initial group of over 130 undergraduate students downloaded 10 suitable photos of themselves from Facebook and ranked them in order of the best to worst likeness. These participants took part in a minute long web cam video of their face and two still photos were also taken (one smiling, one neutral). Sixteen participants who did not know the students watched the webcam videos and afterwards ranked the Facebook photos in order of resemblance to the person they had seen in the video. A further 73 participants were then recruited to complete an online face matching test. Results of the study show that the unfamiliar participants chose a different set of ‘good likeness’ images  compared to those that people had selected of themselves. Surprisingly, the images selected by strangers also led to better performance on the online face matching test. The size of the advantage in other-selection over self-selection was quite large – self-selected images were matched seven per cent less accurately compared to other-selected images. Dr White said: “It seems counter-intuitive that strangers who saw the photo of someone’s face for less than a minute were more reliable at judging likeness. However, although we live with our own face day-to-day, it appears that knowledge of one’s own appearance comes at a cost. Existing memory representations interfere with our ability to choose images that are good representations or faithfully depict our current appearance. “Interestingly we also noted there were better results when people were smiling in the photos. It is interesting that current passport guidelines prohibit smiling in photographs because this ‘distorts the normal facial features’. Given that faces are generally pictured smiling, and these images are rated as being more like familiar faces, it may be beneficial to permit expression in passport photographs.” Story Source: The above post is reprinted from materials provided by British Psychological Society (BPS). Note: Materials may be edited for content and length. Journal Reference: David White; Amy L Burton; Richard I Kemp. Not looking yourself: The cost of self-selecting photos for identity verification. British Journal of Psychology, 2015 DOI: 10.1111/bjop.12141

Custom Print Your Walls!

 

Posted: 24 Jun 2015 05:15 AM PDT

How often have you thought about painting your favorite superhero or secret fantasy on the wall across your bed? Well, with the innovative Printtex Mobile Wall Printer, peeling wallpapers and boring stencils will be a thing of the past. It has the ability to transfer digital pictures onto your wall, with limitless possibilities. Working on the principles akin to an ink-jet printer, two coordinate-sensors are used to limit the print area.

Controlled with your tablet, laptop or smartphone, you can upload and print your desired design on your wall. The printer aligns and prints within the selected area and prints each color tone separately. The sensors on the edge guide the printer and ensure precise printing.

Like the judges of the 2015 iF Design Awards opine, this design showcases the “Intelligent use of the inkjet technology to make the wall as a sheet of paper.”

Designer: Benjamin Loinger

 

New tech could find tiny RNA cancer beacons in blood

 

Tue, 06/23/2015 - 11:40am Nicole Casal Moore, University of Michigan   University of Michigan researchers have developed a technique that allows them to efficiently identify snippets of genetic information called microRNAs in blood. The advance could one day lead to a way to scan for multiple types of cancer at once with a simple blood test. In this illustration, the red, blue and black strands represent different microRNAs that, in the new technique, attach and detach to DNA, which is gray in the image. The DNA glows fluorescent when an RNA attaches and the particular pattern of blinking tells the researchers which microRNA has attached. Image: MolGraphicsCancerous tumors cast off tiny telltale genetic molecules known as microRNAs and Univ. of Michigan researchers have come up with an efficient way to detect them in blood. The researchers say their approach could open the door to a single, inexpensive blood test to simultaneously screen for multiple types of cancer—eventually perhaps more than 100 different kinds. "This could lead to technology that enables earlier detection in individuals at risk for cancer, earlier detection of recurrences in cancer survivors, and also better and earlier assessment of how well cancer therapies are working in patients," said Dr. Muneesh Tewari, the Ray and Ruth Anderson-Laurence M. Sprague Memorial research professor of internal medicine at the U-M Medical School and an associate professor of biomedical engineering in the College of Engineering. It could be years, if not a decade, before this could be available for routine clinical use. But the researchers have high hopes for their ultrasensitive technique that can pick out a single one of these nanoscale snippets in a speck of fluid. "What we have done is develop a new paradigm, a new principle for detecting any sort of RNA in blood," said Nils Walter, professor of chemistry and biophysics in the U-M College of Literature, Science, and the Arts. Walter and Tewari are the senior authors of a study on the work published in Nature Biotechnology. RNA stands for ribonucleic acid, a class of molecule whose members play important roles in building living things from their DNA blueprints. For decades, scientists thought RNA was mainly a messenger: It ferries genetic information from DNA to the sites where cells make proteins—the workhorse molecules that essentially carry out the directions encoded in our genes. But when scientists finished sequencing the human genome around 2003, they learned that 90 percent of it contains directions for making RNA. And most of that RNA is not the messenger kind that helps make proteins. "The field of biochemistry is about 100 years old," Walter said. "And for the longest time, we were focusing on proteins. It is almost as if we were studying the wrong thing. "RNA is profoundly important for understanding and manipulating mammalian and human life, yet it is arguably the least studied genetic material in the mammalian cell. We're just at the beginning of big discoveries of its functions." MicroRNA molecules, for example, are short strands that can bind to the messenger RNA, intercepting the dispatch and preventing bits of genetic code from being put into action. More than 1,000 varieties exist in our bodies. They directly or indirectly control virtually all major life processes, the researchers say. Having too little or too much of a particular microRNA can fuel tumor growth. Cancerous cells are descendent from haywire healthy ones, so they have microRNA in them too. The tiny strands of genetic material have been detected in blood before (though not very efficiently) and scientists have several hypotheses about how they get there. They may be released when a cancerous cell dies and breaks down. And cells, including cancerous ones, may communicate with one another through microRNAs they send into the bloodstream to act as hormones. Blood-borne microRNAs from both mechanisms would be the cancer beacons the new technique could efficiently detect in patients, the researchers say. In their experiments, they coated a glass slide with molecules called "capture probes" that would grab onto microRNAs in their vicinity. Then, in different trials, they dropped onto the slide samples of solutions containing five different microRNAs. In one case, the solution that carried the microRNAs was human blood serum—the fluid component with the blood cells removed. To tell them RNA had been captured by one of the probes, they relied on a third type of molecule—fluorescent DNA strands that bind to the microRNA and emit light when they do. Only specific DNA sequences will bind to particular RNAs, so by varying the arrangement of the building blocks that make the DNA, the researchers engineered strands that would attach to the different microRNAs. What makes their method unique is that the DNA and RNA connect so weakly they don't stay stuck. DNA strings latch onto and detach from RNA in particular rhythms. When the researchers observe this through a super-sensitive fluorescence microscope, it looks like a firefly blinking. They can confirm the capture of different microRNAs based on the blink rate—its "kinetic fingerprint." Although microRNAs have been detected in blood serum before, this approach is more direct and suffers virtually no false positives. Source: University of Michigan

World’s first full-color, flexible, skin-like display

 

Wed, 06/24/2015 - 12:30pm University of Central Florida   Dr. Chanda used an iconic National Geographic photographic of an Afghan girl to demonstrate the color-changing abilities of the nanostructured reflective display developed by his team. Image: University of Central Florida Imagine a soldier who can change the color and pattern of his camouflage uniform from woodland green to desert tan at will. Or an office worker who could do the same with his necktie. Is someone at the wedding reception wearing the same dress as you? No problem—switch yours to a different color in the blink of an eye. A breakthrough in a Univ. of Central Florida lab has brought those scenarios closer to reality. A team led by Prof. Debashis Chanda of UCF's NanoScience Technology Center and the College of Optics and Photonics (CREOL) has developed a technique for creating the world's first full-color, flexible thin-film reflective display. Chanda's research was inspired by nature. Traditional displays like those on a mobile phone require a light source, filters and a glass plates. But animals like chameleons, octopuses and squids are born with thin, flexible, color-changing displays that don't need a light source—their skin. "All manmade displays—LCD, LED, CRT—are rigid, brittle and bulky. But you look at an octopus, they can create color on the skin itself covering a complex body contour, and it's stretchable and flexible," Chanda said. "That was the motivation: Can we take some inspiration from biology and create a skin-like display?" As detailed in Nature Communications, Chanda is able to change the color on an ultrathin nanostructured surface by applying voltage. The new method doesn't need its own light source. Rather, it reflects the ambient light around it. A thin liquid crystal layer is sandwiched over a metallic nanostructure shaped like a microscopic egg carton that absorbs some light wavelengths and reflects others. The colors reflected can be controlled by the voltage applied to the liquid crystal layer. The interaction between liquid crystal molecules and plasmon waves on the nanostructured metallic surface played the key role in generating the polarization-independent, full-color tunable display. His method is groundbreaking. It's a leap ahead of previous research that could produce only a limited color palette. And the display is only about few microns thick, compared to a 100-micron-thick human hair. Such an ultrathin display can be applied to flexible materials like plastics and synthetic fabrics. The research has major implications for existing electronics like televisions, computers and mobile devices that have displays considered thin by today's standards but monstrously bulky in comparison. But the potentially bigger impact could be whole new categories of displays that have never been thought of. "Your camouflage, your clothing, your fashion items - all of that could change," Chanda said. "Why would I need 50 shirts in my closet if I could change the color and pattern?" Researchers used a simple and inexpensive nano-imprinting technique that can produce the reflective nanostructured surface over a large area. "This is a cheap way of making displays on a flexible substrate with full-color generation," Chanda said. "That's a unique combination." Source: University of Central Florida

Swiss Pocket Knife

 

Old model

 

Newest model