New Brain Death Pathway In Alzheimer’s Identified

Findings of team led by the Arizona State University (ASU) scientists offer hope for therapies targeting cell loss in the brain, an inevitable and devastating outcome of Alzheimer’s progression
Alzheimer’s disease tragically ravages the brains, memories and, ultimately, personalities of its victims. Now affecting 5 million Americans, Alzheimer’s disease is the sixth-leading cause of death in the U.S., and a cure for Alzheimer’s remains elusive, as the exact biological events that trigger it are still unknown.

In a new study, Arizona State University-Banner Health neuroscientist Salvatore Oddo and his colleagues from Phoenix’s Translational Genomics Research Institute (TGen) — as well as the University of California, Irvine, and Mount Sinai in New York — have identified a new way for brain cells to become fated to die during Alzheimer’s disease. The research team has found the first evidence that the activation of a biological pathway called necroptosis, which causes neuronal loss, is closely linked with Alzheimer’s severity, cognitive decline and extreme loss of tissue and brain weight that are all advanced hallmarks of the disease.

We anticipate that our findings will spur a new area of Alzheimer’s disease research focused on further detailing the role of necroptosis and developing new therapeutic strategies aimed at blocking it,” said Oddo, the lead author of this study, and scientist at the ASU-Banner Neurodegenerative Disease Research Center at the Biodesign Institute and associate professor in the School of Life Sciences.

Necroptosis, which causes cells to burst from the inside out and die, is triggered by a triad of proteins. It has been shown to play a central role in multiple sclerosis and Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS), and now for the first time, also in Alzheimer’s disease.

There is no doubt that the brains of people with Alzheimer’s disease have fewer neurons,” explained Oddo. “The brain is much smaller and weighs less; it shrinks because neurons are dying. That has been known for 100 years, but until now, the mechanism wasn’t understood.
The findings appear in the advanced online edition of Nature Neuroscience.


Dissolvable Metal Supports for 3D Printing

Support for a visiting professor plus an off-the-cuff remark have led an Arizona State University (ASU) researcher to develop what could be the Holy Grail solution to speeding up the end-to-end process of metal 3D printing.

Owen Hildreth, ASU assistant professor of 3D Nanofabrication, was developing new approaches to reactive silver ink production when he thought he’d sit in on talks regarding the soon-to-be-opened ASU Polytechnic Manufacturing Research and Innovation Hub. One of the speakers, Timothy Simpson, was describing the practical challenges of setting up an additive manufacturing (AM) lab.

Combining a mechanical engineering degree (applied to five years’ work in the 2D printing industry) with a Ph.D. in nanofabrication materials engineering, Hildreth just may have been in the perfect position to bring a fresh perspective to the metal support problem. In contrast to the use of mechanical tools such as wire-EDM equipment, his concept would cause certain areas of a metal AM part to react chemically when immersed in a corrosive solution. The goal was to produce controlled degradation that would literally eat away the supports but leave the actual part virtually intact.

However, because multi-material 3D printing systems are not yet widely available, Hildreth also investigated ways to selectively remove the supports of powder-bed-type metal AM parts. Starting with a simple design for demonstration — a small 17-4 stainless steel cylinder 3D-printed with a single row of 100-micron-diameter needle-like supports — he tested two possible approaches.

In the first one, termed direct dissolution, the part was heat-treated (annealed) while packed with sodium ferrocyanide; this step precipitated out much of the protective chromium carbide, rendering the no-longer-stainless steel susceptible to chemical etching. The latter process was successful, but the part itself experienced significant etching, which continued the longer the part was allowed to sit in the solution.


Massive Use Of Nanoparticles Found In Popular Foods

Popular lollies, sauces and dressings have been found to contain nanotechnology that the national food regulator has long denied is being widely used in Australia’s food supply.

For many years, Food Standards Australia and New Zealand (FSANZ) has claimed there is “little evidence” of nanotechnology in food because no company had applied for approval. It has therefore not tested for nor regulated the use of nanoparticles. Frustrated at the inertia, environment group Friends of the Earth commissioned tests that found potentially harmful nanoparticles of titanium dioxide and silica in 14 popular products, including Mars’ M&Ms, Woolworths white sauce and Praise salad dressing.

nanoparticles found in foodNanoparticles of silica found in Maggi‘s Roast Meat Gravy

FSANZ kept saying there’s no evidence of it, we’re not going to do any testing. But all 14 samples came back positive, indicating widespread use of nanoparticles in foods in Australia,” said the group’s emerging tech campaigner, Jeremy Tager. “Everybody would want to think food is tested and assured to be safe before it hits supermarket shelves. FSANZ is conducting a living experiment with people. It has inexcusably failed in its role as a regulator.

(A human hair is about 100,000 nanometers wide. Nanoparticles are typically less than 100 nanometres and are used to stretch the shelf life and improve the texture of food).

There is no conclusive evidence that nano-titanium dioxide, which whitens and brightens, and nano-silica, which prevents caking, are completely safe to eat. They have been shown to interfere with the immune system and cause cell damage.

The lab test of the 14 supermarket goods, which also included Eclipse chewy mints, Old El Paso taco mix, and Moccona Cappuccino, was conducted by a world-class nanotechnology research facility at Arizona State University.The Food Standards code does not require nanoparticles to be declared on labelling. Nano-titanium dioxide (E171) can be simply described as the conventional-sized type and as “Colour (171)“. Nano-silica (E551) can be listed as the conventional version and as “Anti-caking agent (551)“. FSANZ told Fairfax Media it had not identified any health impacts linked with the consumption of the two types of nanoparticles.


Fuel Cell Electrodes 7 Times More Efficient

A new fabrication technique that produces platinum hollow nanocages with ultra-thin walls could dramatically reduce the amount of the costly metal needed to provide catalytic activity in such applications as fuel cells. The technique uses a solution-based method for producing atomic-scale layers of platinum to create hollow, porous structures that can generate catalytic activity both inside and outside the nanocages. The layers are grown on palladium nanocrystal templates, and then the palladium is etched away to leave behind nanocages approximately 20 nanometers in diameter, with between three and six atom-thin layers of platinum. Use of these nanocage structures in fuel cell electrodes could increase the utilization efficiency of the platinum by a factor of as much as seven, potentially changing the economic viability of the fuel cells.

A transmission electron microscope image shows a typical sample of platinum cubic nanocages

We can get the catalytic activity we need by using only a small fraction of the platinum that had been required before,” said Younan Xia, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. Xia also holds joint faculty appointments in the School of Chemistry and Biochemistry and the School of Chemical and Biomolecular Engineering at Georgia Tech. “We have made hollow nanocages of platinum with walls as thin as a few atomic layers because we don’t want to waste any material in the bulk that does not contribute to the catalytic activity.
The research – which also involved researchers at the University of Wisconsin-Madison, Oak Ridge National Laboratory, Arizona State University and Xiamen University in China – was reported in the July 24 issue of the journal Science.


How To Construct Innovative Nanoforms From DNA Origami

DNA, the molecular foundation of life, has new tricks up its sleeve. The four bases from which it is composed snap together like jigsaw pieces and can be artificially manipulated to construct endlessly varied forms in two and three dimensions. The technique, known as DNA origami, promises to bring futuristic microelectronics and biomedical innovations to market. Hao Yan, a researcher at Arizona State University’s Biodesign Institute (ASU), has worked for many years to refine the technique. His aim is to compose new sets of design rules, vastly expanding the range of nanoscale architectures generated by the method. In new research, a variety of innovative nanoforms are described, each displaying unprecedented design control. Yan directs the  Biodesign’s Center for Molecular Design and Biomimetics. In the current study, complex nano-forms displaying arbitrary wireframe architectures have been created, using a new set of design rules.


The images show the scaffold-folding paths for
A) star shape
B) 2-D Penrose tiling
C) 8-fold quasicrystalline 2-D pattern
D) waving grid.
E) circle array.
F) fishnet pattern
G) flower and bird design
The completed nanostructures are seen in the accompanying atomic force microscopy images.


Earlier design methods used strategies including parallel arrangement of DNA helices to approximate arbitrary shapes, but precise fine-tuning of DNA wireframe architectures that connect vertices in 3D space has required a new approach,” Yan says. Yan has long been fascinated with Nature’s seemingly boundless capacity for design innovation. The new study describes wireframe structures of high complexity and programmability, fabricated through the precise control of branching and curvature, using novel organizational principles for the designs. (Wireframes are skeletal three-dimensional models represented purely through lines and vertices.) The resulting nanoforms include symmetrical lattice arrays, quasicrystalline structures, curvilinear arrays, and a simple wire art sketch in the 100-nm scale, as well as 3D objects including a snub cube with 60 edges and 24 vertices and a reconfigurable Archimedean solid that can be controlled to make the unfolding and refolding transitions between 3D and 2D.

The research appears in the advanced online edition of the journal Nature Nanotechnology.


Low-Cost, Ultra Fast DNA Reader

A team of scientists from Arizona State University’s Biodesign Institute and IBM’s T.J. Watson Research Center have developed a prototype DNA reader that could make whole genome profiling an everyday practice in medicine.
DNA readerOur goal is to put cheap, simple and powerful DNA and protein diagnostic devices into every single doctor’s office,” said Stuart Lindsay, an ASU physics professor and director of Biodesign’s Center for Single Molecule Biophysics. Such technology could help usher in the age of personalized medicine, where information from an individual’s complete DNA and protein profiles could be used to design treatments specific to their individual makeup.

The device is sensitive enough to distinguish the individual chemical bases of DNA (known by their abbreviated letters of A, C, T or G) when they are pumped past the reading head.

Proof-of-concept was demonstrated, by using solutions of the individual DNA bases, which gave clear signals sensitive enough to detect tiny amounts of DNA (nanomolar concentrations), even better than today’s state-of-the-art, so called next-generation DNA sequencing technology. Making the solid-state device is just like making a sandwich, just with ultra high-tech semiconductor tools used to slice and stack the atomic-sized layers of meats and cheeses like the butcher shop’s block. The secret is to make slice and stack the layers just so, to turn the chemical information of the DNA into a change in the electrical signal.


Mimic Nature To Build Man-made Molecular Systems

Using molecules of DNA like an architectural scaffold, Arizona State University (ASU) scientists, in collaboration with colleagues at the University of Michigan, have developed a 3-D artificial enzyme cascade that mimics an important biochemical pathway, a major breakthrough for future biomedical and energy applications.

Remaking an artificial enzyme pair in the test tube and having it work outside the cell is a big challenge for DNA nanotechnology. To meet the challenge, they first made a DNA scaffold that looks like several paper towel rolls glued together. Using a computer program, they were able to customize the chemical building blocks of the DNA sequence so that the scaffold would self-assemble. Next, the two enzymes were attached to the ends of the DNA tubes. In the middle of the DNA scaffold, a research team led by ASU professor Hao Yan affixed a single strand of DNA, with the molecule called NAD+ tethered to the end like a ball and string. Yan refers to this as a swinging arm, which is long, flexible and dexterous enough to rock back and forth between the enzymes to carry out a chemical reaction

We look to Nature for inspiration to build man-made molecular systems that mimic the sophisticated nanoscale machineries developed in living biological systems, and we rationally design molecular nanoscaffolds to achieve biomimicry at the molecular level,” Yan said, who holds the Milton Glick Chair in the ASU Department of Chemistry and Biochemistry.
An even loftier and more valuable goal is to engineer highly programmed cascading enzyme pathways on DNA nanostructure platforms with control of input and output sequences. Achieving this goal would not only allow researchers to mimic the elegant enzyme cascades found in nature and attempt to understand their underlying mechanisms of action, but would facilitate the construction of artificial cascades that do not exist in nature,” said Yan.
The findings were published in the journal Nature Nanotechnology.


A research team at Arizona State University’s Biodesign Institute have launched an ambitious new project, designed to attack nicotine dependence in a radically new way. A chemical component present in the nightshade family of plants is one of the world’s most tenaciously addictive substances. It is the nicotine contained in tobacco and found in high concentrations in cigarettes. Smoking remains a global scourge; in the U.S. it is the leading source of preventable death. Chang, an immunologist, has been developing a method for incorporating key vaccine components onto self-assembling, nanoscale carrier molecules.

The DNA nanostructure enables rational design and construction of synthetic vaccines, because of its precision control over the placement of various antigenic components,” Chang says. “This approach may offer a new strategy to improve the efficacy of many different vaccines.”


Synthetic Nano-Engineered Vaccines

Scientists at the Biodesign Institute at Arizona State University have turned to a promising field called DNA nanotechnology to make an entirely new class of synthetic vaccines. In a study published in the journal Nano Letters, Biodesign immunologist Yung Chang joined forces with her colleagues, including DNA nanotechnology innovator Hao Yan, to develop the first vaccine complex that could be delivered safely and effectively by piggybacking onto self-assembled, three-dimensional DNA nanostructures.

When Hao treated DNA not as a genetic material, but as a scaffolding material, that made me think of possible applications in immunology,” said Chang, an associate professor in the School of Life Sciences and a researcher in they Biodesign Institute’s Center for Infectious Diseases and Vaccinology. “